Open Access

Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)

  • Authors:
    • Leyu Ai
    • Na Yi
    • Chunhan Qiu
    • Wanyi Huang
    • Keke Zhang
    • Qiulian Hou
    • Long Jia
    • Hui Li
    • Ling Liu
  • View Affiliations

  • Published online on: March 8, 2024
  • Article Number: 46
  • Copyright: © Ai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis‑related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis‑related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.

1. Introduction

Breast cancer, a malignancy arising from the epithelial cells of the breast, has witnessed a steady increase in incidence over the years (1). As per the 2020 Global Cancer Statistics Report published in CA: A Cancer Journal for Clinicians, breast cancer surpassed lung cancer to become the world's most prevalent type of cancer in 2020 (2). In that year, an estimated 2.3 million new breast cancer cases were diagnosed, representing 11.7% of all global cancer cases, and 685,000 individuals succumbed to the disease, accounting for 6.9% of global cancer-related deaths (2). Among the types of cancer affecting females, breast cancer stands out with a quarter of the incidence rate and a sixth of the mortality rate, ranking first in terms of incidence in 159 countries and mortality in 110 countries (2). The mainstay of treatment for breast cancer is surgical excision, radiotherapy and adjuvant targeted therapies; however, clinical studies have found that the long-term use of this treatment does not improve patient survival (3). In light of these findings, regulated cell death (RCD) has emerged as a promising avenue for both breast cancer prevention and treatment strategies.

In 2018, the Cell Death Committee refined the definition of RCD by emphasizing its process mechanisms and updating the classification system (4). RCD encompasses a diverse array of developmental and immunological pathways that culminate in distinct modes of cell demise, resulting in varied morphological transformations and immunological consequences (5). This type of cell death can occur intrinsically, without the interference of external factors, serving as an inherent component of physiological programs, such as development or tissue renewal (6,7). This entirely physiological form of RCD is often referred to as programmed cell death. However, RCD can also arise from disruptions in the intracellular or extracellular microenvironment when these disturbances are too severe or prolonged, exceeding the capacity of adaptive responses to maintain cellular homeostasis (8). Oxidative stress, characterized by the generation of reactive oxygen species (ROS), has been implicated as a potential trigger for various forms of RCD. The production of ROS and the effectiveness of antioxidant defenses are reportedly influenced by the surrounding environment (5). In recent years, research on RCD in cancer has increasingly focused on modes, such as cuproptosis, ferroptosis, pyroptosis, immunogenic cell death and autosis. Therefore, the present review primarily discusses and summarizes the regulatory mechanisms, relevant genes and potential drugs associated with cuproptosis, ferroptosis, pyroptosis and other such modes of RCD in the context of breast cancer.

2. Cuproptosis and breast cancer

Copper (symbol, Cu) serves as an essential cofactor for all living organisms, with intracellular levels meticulously maintained within a narrow range. It plays a pivotal role in various physiological processes, including mitochondrial respiration, antioxidant activity and macromolecular biosynthesis. However, exceeding the threshold of homeostatic mechanisms can induce detrimental effects, regardless of whether copper levels are deficient or excessive (9-11). Cuproptosis, a recently discovered cell death pathway, arises specifically from copper overload and operates independently of other known death mechanisms. Copper ions directly bind to lipoproteins within the tricarboxylic acid cycle (TCA) metabolic pathway, causing anomalous aggregation and interfering with the iron-sulfur cluster scaffold protein in the respiratory complex. This disruption culminates in a proteotoxic stress response, ultimately leading to cell death (12-15).

Cuproptosis is distinguished from other types of RCD

Cuproptosis, a unique form of RCD, is specifically induced by copper ion carriers. Notably, inhibitors targeting known cell death pathways, including ferroptosis, necrosis, apoptosis and oxidative stress, exhibit a limited ability to prevent copper ion carrier-induced cell death. This distinct mechanism significantly differentiates cuproptosis from traditional modes of cell death, such as apoptosis and necroptosis. Mitochondrial respiration plays a crucial role in the regulation of cuproptosis. Treatment with mitochondrial antioxidants, fatty acids and inhibitors of mitochondrial function significantly influences copper ion carrier sensitivity, suggesting dependence on mitochondrial activity rather than adenosine triphosphate (ATP) production (16). Key genes contributing to copper-induced death include FDX1 and six genes involved in protein S-acylation, all essential for mitochondrial aerobic metabolism. The knockdown of FDX1 (encoding a protein converting divalent copper ions to toxic monovalent forms) and six lipoylated protein genes (LIPT1, DLD, LIAS, DLAT, PDHA1 and PDHB) has been shown to successfully rescue cells from copper ion-mediated death (16). FDX1 acts as an upstream regulator of protein lipoylation, a conserved lysine post-translational modification limited to four enzymes within metabolic complexes regulating carbon entry into the TCA cycle. It has been established that copper directly binds and induces the oligomerization of lipoylated DLAT. Notably, FDX1 deletion eliminates protein lipoylation, preventing copper binding by DLAT and DLST, indicating the critical role of the lipoyl moiety in copper binding. This unique death mechanism observed in cuproptosis aligns with observations in a genetic model of copper homeostasis dysregulation. Studies using a mouse model of Wilson's disease further suggest that copper overload induces cellular effects identical to those triggered by copper ion carriers, confirming the shared mechanism between copper homeostasis dysregulation and copper ion carrier-induced cell death (17).

Mechanisms involved in cuproptosis

While cuproptosis holds promise, several aspects remain enigmatic. The specific roles of key factors, such as FDX1 require further investigation. Additionally, the mechanisms underlying cuproptosis inhibition in healthy cells are unclear. Furthermore, previous studies suggest that hte various possible cuproptosis-related mechanisms require better integration. Finally, characteristic morphological and molecular changes in cuproptosis-affected cells have not been fully described (18-20).

Copper, crucial for enzymes, necessitates meticulous control at low levels for normal physiological function. Studies highlight its role in cancer progression (21-25). Notably, patients with breast cancer exhibit significantly higher serum levels of copper compared to the controls, suggesting its potential in early detection and monitoring. In triple-negative breast cancer (TNBC), inhibiting mitochondrial copper forces tumor cells to switch from respiration to glycolysis, reducing energy production and ultimately hindering tumor growth and improving prognosis (26-30). The novel concept of cuproptosis sheds light on the copper-cancer link. Elesclomol, a copper ion carrier, binds to environmental copper and delivers it into cells, triggering cell death. This approach may be most effective in cancers highly expressing mitochondrial lipoylated proteins and relying heavily on respiration. Moreover, it could be particularly useful in apoptosis-resistant cancers, providing a novel strategy with which to eliminate cancer cells by leveraging the unique properties of copper (31,32). Building upon the anticancer properties of copper, chelators and carriers are currently undergoing preclinical and clinical evaluations in various tumor types. Copper chelation therapies, such as tetrathiomolybdate and ATN-224 have reached phase II clinical trials in breast cancer. Disulfiram, a copper ion carrier, is under phase II investigation for malignant glioma, while elesclomol holds promise for the treatment of melanoma in phase II trials (33-36).

Relevant targets for cuproptosis in breast cancer

Intracellular copper overload has recently been linked to a novel form of cell death known as cuproptosis. Independent of traditional pathways, cuproptosis does not activate caspase-3 and remains unaffected by apoptosis inhibitors (15). Genes associated with this process include FDX1, LIPT1, LIAS, DLD, DBT, GCSH, DLST, DLAT, PDHA1, PDHB, SLC31A1, ATP7A and ATP7B. These genes primarily regulate processes, such as glycolysis, the TCA cycle, and steroid and vitamin D metabolism. Notably, SLC31A1 facilitates copper uptake, while ATP7A and ATP7B are responsible for copper efflux, maintaining intracellular copper levels (37-41). The overexpression of SLC31A1 and the deletion of ATP7B can increase susceptibility to cuproptosis, whereas the knockdown of nine specific genes (FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, GCSH and DBT) confers resistance (15). While the role of copper in breast cancer, particularly its impact on the immune microenvironment and immunotherapy, has been well-established (42), the association between seven key cuproptosis-associated genes and breast cancer remains unexplored. These genes include PGK1 (mitochondrial metabolism and tumorigenesis), SLC family members SLC52A2 and SLC16A6 (metabolic transport), SEC14L2 (vitamin E uptake), RAD23B (nucleotide excision repair and apoptosis), CCL5 (inflammatory cell migration) and MAL2 (transcytosis in hepatocellular carcinoma) (43-58).

Song et al (59) analyzed the protein expression of the cuproptosis-related genes, FDX1, LIPT1, MTF1, DLD, DLAT, PDHA1 and PDHB, in breast cancer tissues and their mRNA expression in cuproposis-inducible breast cancer cell models. Notably, RAD23B expression was found to be positively associated with breast cancer progression, drug resistance and a poor prognosis of patients with breast cancer. Notably, both PD1 and PDL1 expression exhibited a positive correlation with RAD23B expression, suggesting that patients with higher RAD23B levels may be more responsive to immune checkpoint blockade therapy targeting the programmed cell death 1 (PD-1)/PD-L1 axis (59).

Recent advances in cuproptosis-related drugs

In addition, the crucial role of cuproptosis in tumor cells presents an opportunity to develop novel anticancer drugs. One such example is the platelet vesicle (PV)-coated cuprous oxide nanoparticle (Cu2O)/TBP-2 cuproptosis sensitization system (PTC). Modified by AIE photosensitizer (TBP-2), Cu2O and PV mimicry, PTC can enhance its long-term blood circulation and tumor targeting ability. Subsequently, PTC is rapidly degraded to release copper ions under acidic conditions and hydrogen peroxide in tumor cells. Under light irradiation, TBP-2 rapidly enters the cell membrane and generates hydroxyl radicals to consume glutathione and inhibit copper efflux. Accumulated copper can cause lipoylated protein aggregation and iron-sulfur protein loss, which result in proteotoxic stress and ultimately, in cuproptosis. PTC inhibits tumor cell proliferation and invasion through cuproptosis. Notably, PTC research, primarily in patients with lung metastases from breast cancer, have shown the significant inhibition of metastatic tumor cell growth and multiplication in the lungs (60). Furthermore, the hyaluronic acid-dopamine (HD)/berberine hydrochloride (BER)/glucose oxidase (GOx)/Cu hydrogel reactor system provides a promising avenue for multiple breast cancer treatments. This system effectively inhibits tumor growth through a combination of approaches: GOx and copper sulfate convert accumulated glucose into hydroxyl radicals within tumor cells, enacting starvation/chemokinetic therapy. Additionally, Cu induces cuproptosis, further hindering tumor cell growth. BER, included as a chemotherapeutic agent, synergizes with the starvation/chemokinetic/cuproptosis modalities. This 'hydrogel multiplicity effect' allows the system to potentially reduce the size of breast cancer pre-operatively, facilitating surgical resection (61). While these novel drugs harness cuproptosis for therapeutic purposes, their clinical efficacy remains to be determined as they are currently limited to biological experiments. However, their potential offers hope for future advancements in breast cancer treatment.

3. Ferroptosis and breast cancer

Ferroptosis proposed by Dixon et al (62) in 2012, is a unique form of cell death distinct from apoptosis and necrosis, triggered by a compound known as RSL3 (62). It is characterized by the iron-dependent accumulation of lipid peroxidation to lethal levels, affecting cellular structures and metabolism. This includes mitochondrial atrophy, increased membrane density, disrupted membrane integrity and the depletion of intracellular NADH (63). Three key mechanisms drive ferroptosis: i) Transferrin and L-glutaminase regulation in cancer cells (64); ii) the depletion of glutathione, leading to glutathione peroxidase 4 (GPX4) inactivation (a core antioxidant enzyme) and the subsequent disruption of the antioxidant system in cancer cells (65); and iii) the peroxidation of unsaturated fatty acids in cell membranes by divalent iron or esterases in cancer cells (66).

Ferroptosis targets in breast cancer

The mammary gland specifically regulates ferroptosis, a type of RCD. Adipocytes, fat cells in the mammary gland, significantly influence breast cancer cell growth, and promote migration and invasion. In breast cancers expressing the ACSL3 gene, adipocytes protect cancer cells from ferroptosis by providing oleic acid, creating a unique tumor microenvironment (67-69). Hypercholesterolemia, high blood cholesterol, promotes breast cancer development and metastasis by resisting ferroptosis directly or through its metabolite, 27-hydroxycholesterol (70,71). When treated with statins, cancer cells may increase their uptake of exogenous cholesterol or boost their cholesterol production, highlighting the need for real-time tumor monitoring in patients with breast cancer taking statins (72). Ferroptosis holds significant relevance to breast cancer, offering potential for clinical screening and prognosis. Sha et al (73) identified the expression of ACSL4, a positive regulator of ferroptosis, as an independent predictor of the pathological complete response to neoadjuvant chemotherapy, with a higher expression suggesting a greater sensitivity. Studies have also shown that GPX4, an antioxidant enzyme, regulates mitochondria-mediated apoptosis in cancer cells through the modulation of EGR1, functioning as a tumor suppressor in well-differentiated breast cancers and potentially serving as a therapeutic target (74). Zhang et al (75) identified long non-coding RNAs (lncRNAs) closely related to ferroptosis through Cox regression analysis, which can accurately predict the prognosis of patients with breast cancer. These lncRNAs, as characteristic molecules of pyroptosis (another form of RCD), may play a role in antitumor immune processes and hold potential as therapeutic targets (76). Current evidence suggests that MTHFD2, a mitochondrial enzyme involved in folate metabolism, is highly expressed in embryos and various tumors. As a potential regulator of ferroptosis in breast cancer, it may serve as a crucial molecular biomarker and a novel therapeutic target for predicting the prognosis of patients with TNBC (77,78). Furthermore, Yadav et al (79) found that breast cancer cells can evade cell death by overexpressing SLC7A11, which resists ferroptosis by influencing the tumor microenvironment. Notably, miR-5096 can target and downregulate SLC7A11, inducing ferroptosis in breast cancer cells and inhibiting tumor growth (79-81). Zhang et al (82) constructed a nomogram based on nine ferroptosis-related genes. These ferroptosis-related genes were significantly associated with the level of immune cell infiltration in patients with breast cancer, suggesting their potential use as therapeutic targets or biomarkers (82-90). Additionally, studies have shown that the deletion of CircRHOT1 inhibits breast cancer cell proliferation and induces apoptosis, while the knockdown of CLCA2, REEP6, SPDEF and CRAT can predict breast cancer prognosis based on metabolic gene classification (91,92). Research on ferroptosis-related regulatory mechanisms and genes is ongoing, holding promise for improved breast cancer screening and treatment. It can be expected that these research findings may translate into clinical applications in the near future.

Related drugs that can induce ferroptosis

Currently, promising drug studies are investigating the potential of targeting ferroptosis, a form of cell death, in the treatment of breast cancer. Several novel drugs have been proposed that act on this pathway to enhance existing therapies. Zhang et al (93) constructed heparanase (HPSE)-driven sequential release nanoparticles, which consisted of β-cyclodextrin-grafted heparin [NLC/H(D + F + S) NPs] co-modified with doxorubicin (DOX), di-ferric iron (Fe2+) and a TGF-β receptor inhibitor (SB431542); co-loading modification effectively enhanced intracellular ROS levels and activated the ferroptosis pathway. The increased production of ROS also triggered apoptosis, reduced an enzyme linked to tumor invasion (MMP-9) and synergized with ferroptosis for the treatment of breast cancer (93). Similarly, polydopamine nanoparticles loaded with iron and DOX exhibit a wide range of anticancer effects (94). Cinnamaldehyde dimers formulated into lipid-like materials deplete glutathione, a key antioxidant, and when combined with the anticancer drug, sorafenib, significantly enhance ferroptosis and trigger a potent immune response in mice, leading to complete tumor eradication (95,96). Erastin@FA-exo, a folic acid-labeled exosome carrying the ferroptosis inducer, erastin, inhibits the expression of GPX4, depleting intracellular glutathione and upregulating cysteine dioxygenase, leading to excessive ROS production, both hallmarks of ferroptosis. This approach effectively reduces the survival of TNBC cells in vivo and exhibits high biocompatibility compared to conventional erastin, potentially reducing side-effects and paving the way for improved clinical applications (97). These novel drugs offer exciting new possibilities for the clinical treatment of breast cancer by harnessing the power of ferroptosis.

Several common clinical drugs have significant inhibitory effects on breast cancer cell growth. For example, metformin reduces the protein stability of SLC7A11 by inhibiting its UFMyation process, and SLC7A11 opposes ferroptosis by affecting the tumor microenvironment to resist the ferroptosis of tumor cells, thereby inhibiting the growth of breast cancer cells (81,82,98). Siramesine and lapatinib initially induce ferroptosis during the death process in breast cancer cells, but this transforms into autophagy after 24 h (99). In this process, ROS production plays a key role, and cystine transport inhibition, ferroportin-1 and transferrin are involved in the induction of ferroptosis (99,100). Everolimus, a targeted therapeutic agent for breast cancer, can also undergo ferroptosis by inducing the activation of the FKBP1A/SLC3A2 axis. The specific mechanism is that its related protein, FK506-binding protein 1A (FKBP1A), binds to SLC3A2 and negatively regulates SLC3A2 expression during the everolimus-induced ferroptosis of breast cancer cells and the promotion of antiproliferative Th9 lymphocytes (101). This finding suggests that everolimus may be more effective in breast cancer patients who are more sensitive to it, potentially increasing the efficacy of chemotherapy and reducing the dose of chemotherapeutic agents needed (101). Ketamine inhibits breast cancer cell proliferation by targeting the KAT5/GPX4 axis to induce ferroptosis (73). Additionally, targeting GPX4 cann enhance the anticancer effects of gefitinib, suggesting that the study of the two drugs together may provide a new direction for clinical treatment (102,103). Simvastatin has been reported to inhibit HMGCR expression and downregulate the mevalonic acid pathway and GPX4, thereby inducing ferroptosis in TNBC cells (104). Holo lactoferrin induces ferroptosis in cancer cells and sensitizes TNBC cells to radiotherapy (105). Holo lidocaine promotes ferroptosis in ovarian and breast cancer cells via the miR-382-5p/SLC7A11 axis (106).

Some common plant extracts have also been found to exert a promoting effect on ferroptosis. For example, curcumin has been shown to significantly downregulate GPX4 and upregulate HO-1, and both HO-1 and GPX4 enhance ferroptosis in breast cancer (71,72,107). Red ginseng polysaccharides, an effective extracted component of ginseng, also promote ferroptosis, inhibit GPX4 expression and exert antitumor effects (108). These findings suggest that ferroptosis may be a novel therapeutic target for breast cancer. DMOCPTL, a derivative of the natural product, chamomile lactone, can directly bind to GPX4 protein to induce GPX4 ubiquitination and induce ferroptosis. This substance effectively inhibits the growth of breast tumors without significant cytotoxicity, rendering it a potential treatment option for patients with TNBC (74). On the whole, the latest research findings on ferroptosis provide new hope for the development of more effective treatments for breast cancer. However, further research is required in order to develop a complete treatment plan that utilizes ferroptosis.

4. Pyroptosis and breast cancer

Pyroptosis, a novel type of RCD distinct from apoptosis, was first proposed by Cookson and Brennan (109) in 2001, as a rapid death mechanism observed in Salmonella-infected macrophages dependent on caspase-1 activation. Gasdermin (GSDM) proteins, the key molecules in pyroptosis, induce cell membrane lysis (110). There are two main categories of pyroptosis mechanisms: Classical and non-classical pathways. The classical pyroptosis pathway is triggered by exogenous or endogenous microbial infections that stimulate the production of inflammasomes. These inflammasomes activate caspase-1 proteins, which in turn disrupt the integrity of the cell membrane. Additionally, this pathway promotes the activation and release of the inflammatory cytokines, interleukin (IL)-1β and IL-18. The combined action of caspase-1 proteins and inflammation leads to pyroptosis (111-113). The non-classical pyroptosis pathway, on the other hand, is mediated by lipopolysaccharide-activated caspase-4/5/11 (114).

Mechanisms and genes involved in pyroptosis in breast cancer

Pyroptosis and its association with tumors have become a prominent research area in recent years, and the present review specifically summarizes the association between pyroptosis and breast cancer. Breast cancer exhibits a unique regulatory mechanism associated with pyroptosis. Mitochondrial uncoupling protein 1, linked to an production of body heat, has a high expression in breast cancer cells. This leads to mitochondrial swelling and autophagy, activating GSDME, stimulating antitumor immunity, and ultimately resulting in pyroptosis. This process inhibits breast cancer cell proliferation and holds potential as a prognostic marker (115-117). PD-L1, exhibiting nuclear transcriptional activity, participates in the pyroptosis pathway and modulates the tumor microenvironment. In breast cancer cells, this manifests as TNF-α activating caspase-8, which, in the presence of GSDMC and hypoxia-activated nPD-L1, converts apoptosis into pyroptosis, leading to tumor necrosis in hypoxic areas (118). As identified in the literature, the dysregulation of numerous pyroptosis genes is associated with breast cancer prognosis. The high expression of CASP6, CASP5, TIRAP, SCAF11, NLRP7, PLCG1, GSDMC, GSDMD and NLRC4 is associated with a poor prognosis, while the high expression of ELANE, CASP9, CASP8, GSDMB, CASP4, CASP1, TNF, NOD1, PYCARD, NLRP6, NLRP3, NLRP2, IL6, NLRP1, IL18 and IL1B is associated with improved outcomes (27,119-130). Furthermore, several genes emerged as potential therapeutic targets for breast cancer. DRD2, for instance, inhibits NF-κB signaling activation by binding to β-arrestin2, downregulating DDX5 and eEF1A2. This combined action suppresses the NF-κB signaling pathway and p65 phosphorylation. Additionally, DRD2 modulates the tumor microenvironment and promotes macrophage M1 polarization, ultimately triggering pyroptosis in breast cancer cells (131). In a previous study, SCAF11 expression was found to be elevated in breast tumor cell lines, and its high levels were shown to be associated with a poor prognosis (120). Silencing SCAF11 using siRNA significantly reduced the proliferation and colony growth of BT549 and T47D breast cancer cell lines. GSEA analysis revealed that SCAF11 co-expressed genes were primarily involved inflammatory and immune-related pathways (131). Moreover, SCAF11 expression exhibited a positive correlation with immune checkpoints, such as PD-L1, B7H3 and PDCD1LG2. Based on these findings, SCAF11, as a pyroptosis regulatory gene, warrants exploration as a potential therapeutic target for breast cancer patients (131).

Anti-breast cancer drugs that can leverage pyroptosis

Research on pyroptosis in breast cancer has led to investigations into the potential of existing drugs to induce this cell death process. DOX exhibits a three-pronged approach: It dose-dependently reduces the viability of MDA-MB-231 and T47D cells, activates caspase-3 through GSDME, induces the accumulation of intracellular ROS, and subsequently stimulates the phosphorylation of JNK and the activation of caspase-3, and culminates in pyroptosis, exerting its anticancer effects (132). Tetraarsenic arsenic hexaoxide exerts its anticancer effects by targeting a crucial factor in breast cancer cells, mitochondrial STAT3. Inhibiting its activation leads to mitochondrial ROS-mediated pyroptosis (133,134). Nigericin, derived from Streptomyces hydrophobicus, triggers pyroptosis in TNBC cells by inducing potassium efflux and subsequent mitochondrial ROS production. This process activates the caspase-1/GSDMD pathway. Moreover, combining nigericin with anti-PD-1 antibodies exhibits synergy in treating advanced triple-negative breast cancer (135). Notably, trimethylamine N-oxide (TMAO), a metabolite produced by the Clostridium genus, induces pyroptosis in tumor cells by activating the endoplasmic reticulum kinase, PERK. This, in turn, enhances CD8 T-cell-mediated antitumor immunity in TNBC models in vivo. As immunotherapy is a crucial option for these patients, the ability of TMAO to boost its efficacy suggests its potential application in the treatment of TNBC (136). Azurocidin-1, a protein originating from neutrophils and predominantly stored in azurophilic granules, exerts its effects on pyroptosis in TNBC cells through the regulation of the pNF-κB/NLRP3/caspase-1/GSDMD axis. The identification of Azurocidin-1 holds promise in the development of novel immunotherapeutic approaches for the treatment of TNBC (137). The treatment of breast cancer cells with docosahexaenoic acid has been found to increase the activation of caspase-1 and GSDMD, enhance the secretion of IL-1β, promote the translocaton of high-mobility group protein B1 (HMGB1) to the cytoplasm and to lead to the formation of membrane pores. These findings suggest that docosahexaenoic acid induces the pyroptosis-programmed death of breast cancer cells and exerts an anti-breast cancer effect (138). Xihuangwan, a traditional Chinese medicine, has been found to induce pyroptosis via the cyclic AMP-activated protein kinase (cAMP)/protein kinase A signaling pathway, and inhibit the proliferation, migration and invasion of breast cancer cells (139). Dihydroartemisinin, a plant extract, promotes the AIM2/caspase-3/DFNA5 axis in breast cancer cells and induces pyroptosis, inhibiting breast cancer growth (140). In addition, Ganoderma lucidum extract (GLE) activates cysteine 3 and further cleaves GSDME proteins to form membrane pores in cell membranes, thereby releasing large amounts of inflammatory factors in breast cancer cells, leading to pyroptosis and inhibiting the growth and multiplication of breast cancer cells. GLE also disrupts multiple steps of tumor metastasis, including adhesion, migration, invasion, colonization and angiogenesis. Overall, GLE offers a potential approach for the treatment of breast cancer that could complement chemotherapy or immunotherapy for cancer metastasis (141).

Current research has identified a novel therapeutic molecule, a bionic nanoparticle of indocyanine green and decitabine, which synergistically upregulates GSDME expression through DNA methylation inhibition and enhances caspase-3-mediated cleavage of GSDME, leading to cancer cell pyroptosis and inhibiting primary breast cancer and distant metastasis (142). Co-assembled carrier-free chemo-photodynamic nanoplatforms (A-C/NPs) of cytarabine (Ara-C) and chlorine e6 (Ce6) can induce tumor cell pyroptosis and enhance the body's immune response to breast cancer. Their specific mechanisms are the following: A-C/NPs trigger GSDME-mediated pyroptosis in a controlled manner via ROS accumulation, and Ara-C stimulates the maturation of cytotoxic T-lymphocytes, synergizing with Ce6-mediated immunogenic cell death to jointly enhance the anticancer effects of A-C/NPs. In a previous study using a mouse model of breast cancer, A-C/NPs were found to markedly inhibit in situ, metastatic and recurrent tumor growth (143). Current research on cellular focalization-related drugs focuses on GSDME cleavage and the regulation of the caspase-1/caspase-3 pathway. Relevant experiments have demonstrated the effectiveness of this approach for breast cancer (74,109,112). However, further studies are warranted to investigate potential adverse effects on the organism and to establish clinical application guidelines, including dosing information. Therefore, advancing the use of pyroptosis-related drugs in breast cancer should prioritize research on potential drawbacks associated with GSDME cleavage and caspase-1/caspase-3 pathway regulation.

5. Other forms of cell death and breast cancer

Current academic research on RCD in breast cancer extends beyond previously mentioned modes to include immunogenic cell death, autophagic cell death and others, all of which can both promote and inhibit the growth and metastasis of breast cancer cells. As regards immunogenic cell death, researchers have found that Trametes robiniophila Murr. (Huaier) increases the release of ATP and HMGB1 by promoting cell surface calreticulin exposure. Its therapeutic effects are linked to endoplasmic reticulum stress through the cAMP/PKR/eIF2α axis, both of which trigger immunogenic cell death in TNBC cells (144). Breast cancer cells produce angiopoietin-like 7 (Angptl7), a tumor-specific factor localized in the perineal regions, which contributes to the formation of necrotic apoptosis and the metastatic dissemination of the tumor core. Functional studies have shown that Angptl7 deficiency allows central necrosis and autophagy, ultimately protecting the growth of breast cancer cells and promoting their metastasis. Mechanistically, Angptl7 promotes vascular permeability and supports perineal positioning vascular remodeling (145). Current research suggests that autophagy can serve as a form of nutritional support for cellular self-repair. However, it may also contribute to tumor dormancy in breast cancer, potentially promoting chemoresistance and relapse (146,147).

6. Co-modulation of conventional chemotherapeutic agents by multiple types of RCD

Role of DOX in various types of RCD in breast cancer

In the present review, the summary of RCD in breast cancer reveals that DOX, a classic antitumor drug, interacts with various cell death pathways. In ferroptosis, DOX downregulates GPX4 and triggers excessive lipid peroxidation through the DOX-Fe2+ complex in the mitochondria, ultimately leading to ferroptosis-mediated cell death. Of note, the combination of ferrostatin-1 and zVAD-FMK effectively regulates ferroptosis and prevents DOX-induced cardiomyocyte death, offering potential therapeutic avenues (148). For pyroptosis, DOX accumulation leads to a cascade of events, beginning with ROS generation. ROS then stimulate the phosphorylation of JNK (specifically p-JNK), which in turn activates caspase-3, a key pyroptosis executioner. Additionally, DOX-induced ROS production also affects the cleavage of caspase-8, further promoting caspase-3 activation. Ultimately, activated caspase-3 cleaves GSDME, triggering the characteristic membrane rupture and pyroptotic cell death in breast cancer cells (132). Furthermore, DOX exhibits a direct interaction with the pyroptosis-associated protein, GSDMD, mitigating the cardiotoxic effects associated with the drug, a finding with potential clinical implications (149,150). Based on these underlying mechanisms, novel technologies have been employed to develop targeted breast cancer drugs that focus on RCD. Several promising therapeutic modalities have emerged.

As previously demonstrated, DOX-loaded hedgehog pathway inhibitor ellagic acid (EA) was combined with Cu2+ to develop nanoscale metal-organic frameworks (EA-Cu) modified by targeted chondroitin sulfate (151). This approach was shown to achieve the inhibition of stemness maintenance by inhibiting the hedgehog pathway through EA, while Cu2+ disrupted mitochondrial metabolism. This combination reduces the stemness characteristics of tumor cells and enhanced the effectiveness of DOX-mediated chemotherapy. The co-action of EA and Cu induces cuproptosis, thereby enhancing anticancer effects and preventing the development of DOX resistance (151). In summary, CS/NPs demonstrate notable antitumor effects by inducing cuproptosis and significantly inhibiting cancer cell stemness, suggesting their potential to overcome resistance to cancer chemotherapy (151).

Emerging therapeutic modalities targeting ferroptosis utilize this interaction. One such modality utilizes degraded bimetallic nanoparticles-7% Fe-doped ZIF-8 encapsulated with DOX, a classical drug used in the treatment of breast cancer. This approach inhibits the growth and metastasis of breast cancer cells by utilizing ferroptosis to induce the production of ROS in cancer cells (152). Several studies have explored strategies with which to mitigate the side-effects of DOX, while harnessing its antitumor effects. For example, isoliquiritin, a natural compound, inhibits the NF-κB signaling pathway, which regulates ferroptosis in breast cancer and improves resistance to DOX (153). Additionally, decreasing the levels of GSDME protein, a key factor in pyroptosis, can minimize DOX-induced cardiotoxicity and pyroptosis in breast cancer cells (132). While DOX itself can induce necroptosis, activating the NF-κB/TNF-α/TNFR/IRF axis further enhances this process, resulting in the SBP-0636457/DOX-induced necrosis of breast cancer cells (154) (Fig. 1).

Adjuvant drugs can also be utilized to modulate the anticancer effects of DOX through the regulation of RCD. It has been shown that plant extracts containing magnoflorine (Mag) significantly enhance the effects of DOX on the induction of autophagy by increasing the expression of light chain 3 (LC3)-II. Notably, combined treatment with DOX and Mag significantly inhibits the activation of PI3K/AKT/mTOR signaling pathway (155). Conversely, it promotes the p38 MAPK pathway, leading to the induction of both autophagy and apoptosis. These findings suggest that Mag may potentiate the anticancer effects of DOX and enhance the sensitivity of breast cancer cells to this chemotherapeutic agent (155). As a cornerstone of breast cancer chemotherapy, the diverse roles of DOX in regulating cell death remain under active investigation. Future research within the academic community is expected to uncover additional functions of doxorubicin and targeted drugs in this context.

RCD and cisplatin

In addition to DOX, cisplatin also exhibits diverse interactions with RCD pathways in breast cancer. As a potent metallochemotherapeutic agent, cisplatin can overcome resistance through various mechanisms. One approach involves the induction of cuproptosis by constructing copper(II) bis(diethyldithiocarbamate) (CuET). This increases CuET distribution in the cytoplasm and cytoskeleton, effectively bypassing cisplatin resistance (156). Furthermore, cisplatin has been shown to induce ferroptosis, another form of RCD, to overcome resistance (157). The overexpression of the ferroptosis driver, SOCS1, inhibits proliferation and promotes ferroptosis in TNBC cells, modulating cisplatin resistance (158). Additionally, inhibiting the ferroptosis-related gene, GPX4, which eliminates ROS crucial for ferroptosis, sensitizes tumor cells to cisplatin. Research using nude mouse models has demonstrated that combining cisplatin with the GPX4 inhibitor, RSL3, significantly reduces tumor growth compared to either treatment alone (159). These findings suggest that GPX4 inhibition suppresses ferroptosis and enhances the anticancer effects of cisplatin. Cisplatin can also promote pyroptosis, another RCD pathway. By upregulating MEG3, it activates the NLRP3 inflammasome, leading to caspase-1-dependent pyroptosis. This activation cleaves GSDMD, releasing fragments that form membrane pores. Moreover, caspase-1 promotes the maturation and secretion of IL-18 and IL-1β, ultimately inducing the focal death of breast cancer cells and exerting antitumor effects (160) (Fig. 2). Notably, cisplatin can also induce autophagy, a cellular self-degradation process. It upregulates several autophagy-related genes, including AMBRA1, ATG3, ATG4C, ATG4D, ATG5, ATG7, ATG13, ATG14, ATG16L2, Beclin1, DRAM1, GABARAP, GABARAPL1, GABARAPL2, HDAC6, IRGM, MAP1LC3B and ULK1 involved in the induction, vesicle nucleation and elongation phases of autophagy, suggesting that it inhibits cell proliferation and growth in breast cancer through multiple RCD mechanisms (161). Overall, these findings suggest that inducing various forms of RCD can effectively reduce cisplatin resistance and enhance its anticancer effects in breast cancer.

7. Comparison and co-action of multiple types of RCD

Specific features of RCD

RCD stands apart from accidental cell death, which results from uncontrolled damage exceeding the survival threshold of a cell. Unlike its chaotic counterpart, RCD is a genetically controlled and orderly process that maintains internal stability (162). The present review showcases the ability of RCD to selectively target tumor cells, hindering their growth and spread. As such, RCD emerges as a promising avenue for cancer therapy.

Comparison of different types of mechanisms for RCD

Various forms of RCD exist, each with unique regulatory mechanisms. Cuproptosis is triggered by the direct interaction of copper with thiooctylated components of the TCA cycle. This interaction leads to the aggregation of these proteins and the depletion of iron-sulfur cluster proteins, inducing proteotoxic stress and, ultimately, cell death (16). By contrast, ferroptosis is characterized by iron-dependent lipid peroxidation damage within the mitochondria, primarily caused by the reduced activity of the GPX4 enzyme (163). Pyroptosis, on the other hand, is activated by external stimuli that induce the formation of inflammatory vesicles. These vesicles activate caspase-1, which disrupts the cell membrane and leads to the release of IL-1β and IL-18 cytokines. The combined action of these cytokines then induces pyroptosis in the affected cell (164) (Fig. 3). Although the detailed mechanisms of each RCD type differ, they all share the characteristic of being initiated by the intrinsic regulatory processes of the cell. Cells that have not initiated these processes remain alive. This understanding highlights the potential of RCD as a novel approach to cancer therapy. Research in this area has already shown promise in improving the accuracy of treatment and patient outcomes.

Oxidative stress: A common mode of causing multiple types of RCD

Oxidative stress, characterized by the accumulation of ROS, plays a critical role in triggering various forms of RCD in cancer cells. Recent studies have shed light on the crucial role of MTF1, a gene associated with cuproptosis. Notably, its expression differs in tumor cells compared to normal cells, and reducing MTF1 levels can elevate ROS production and initiate cuproptosis (165). Similarly, the buildup of ROS is crucial for ferroptosis, another form of RCD. Polyunsaturated fatty acids, a hallmark of ferroptosis, are produced when ROS attack the double bonds in lipids (166). For pyroptosis, ROS trigger the activation of the NLRP3 inflammasome, which initiates and activates NLRP3 synthesis. This inflammasome acts as the key player in initiating pyroptosis (167). In summary, oxidative stress plays a pivotal role in triggering various forms of RCD in cancer cells. This understanding opens new avenues for developing synergistic cancer therapies that leverage multiple RCD modalities.

RCD and conventional chemotherapeutic agents

As aforementioned, the induction of cuproptosis, ferroptosis and pyroptosis can enhance the anticancer properties of drugs, such as DOX and cisplatin, while reducing their resistance and side-effects. This research also suggests the potential to develop predictive models based on lncRNAs associated with cuproptosis. These models could help determine the sensitivity of patient with breast cancer to various chemotherapeutic agents (such as lapatinib, phenelzine, vincristine and etanercept), aiding in the selection of personalized treatment regimens (168). Furthermore, the protein, RelB, provides evidence for the influence of ferroptosis on chemotherapeutic response. RelB promotes resistance to tamoxifen by upregulating GPX4, an enzyme that inhibits ferroptosis (169). Similarly, miR-155-5p supports the role of pyroptosis in response to therapy. In vivo research has demonstrated that decreasing miR-155-5p levels triggers pyroptosis and enhances the effectiveness of the drug, cetuximab, against TNBC cells (170). These findings suggest that RCD research can not only lead to the discovery of new drugs, but may also shed light on the anticancer potential and resistance mechanisms of existing drugs.

Interactions of forms of RCD

There is a potential association between various RCD modes. Cuproptosis and ferroptosis regulators exhibit the same mutation frequency in breast cancer. As previously demonstrated, the knockdown of the ferroptosis regulator, ATF2, in breast cancer cells (MCF7) resulted in marked changes in cuproptosis regulators (DLST, GCSH, PDHA1, LIPT1 and DLD) (171). Furthermore, the unsupervised clustering of cuproptosis and ferroptosis regulators identified three distinct copper/ferroptosis regulator clusters named CuFecluster A, B and C. These three regulator clusters have different biological functions. The three regulatory factor clusters have distinct biological functions, which strengthen the experimental basis for using RCD for tumor therapy. CuFecluster B is associated with the full activation of immunity, including the B-cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, antigen processing and presentation, cytokine-cytokine receptor interactions and chemokine signaling pathway. Additionally, CuFecluster B is enriched in various activated immune cells and is classified as an immunoinflammatory phenotype. CuFecluster A is associated with various cellular proliferative processes, particularly mismatch repair, DNA replication and the cell cycle. Notably, CuFecluster A is more strongly associated with innate immune cells (including myeloid-derived suppressor cells, eosinophils, natural killer cells, monocytes, mast cells and macrophages). Finally, CuFecluster C exhibits a limited association with immune cells and suppresses immune responses, consistent with the main features of the immune desert phenotype (171). Different clusters of regulatory factors can be harnessed, therefore, to open new avenues for future breast cancer therapy. In conclusion, while this study has summarized the interactions and derived functions of cuproptosis and ferroptosis in breast cancer, associations with other RCDs are still under investigation. Nevertheless, this work provides valuable insights for exploring the relationships between other regulatory death pathways in the future, potentially leading to new benefits for breast cancer patients.

Summarizing the role of various forms of RCD in tumor cells in breast cancer reveals that various RCD pathways can inhibit cancer cell proliferation and invasion. Additionally, they can reduce resistance to conventional chemotherapeutic drugs. Combining multiple RCD modalities in breast cancer therapy holds promise for synergistic effects and offers a promising new avenue for treatment.

8. Importance of multiple types of RCD for breast cancer

Importance of cuproptosis for breast cancer cells

It has been established that cuproptosis-associated genes can predict the prognosis of patients with breast cancer and provide information about the immune microenvironment. Cox regression analyses identified high expression of the cuproptosis-associated gene, SLC31A1, as an independent prognostic factor for a shorter overall survival. Additionally, a high SLC31A1 expression has been shown to be associated with dysregulated immune responses; specifically, it has been shown to be negatively associated with the level of infiltration of CD8 T-cells and activated natural killer cells (53). Furthermore, targeting cuproptosis with existing drugs may provide new avenues for the treatment of breast cancer. Zinc pyrithione (ZnPT), typically used for fungal treatment, promotes the aggregation of DLAT both in vitro and in vivo. DLAT is a biomarker of cuproptosis and ZnPT disrupts copper homeostasis, eventually leading to cuproptosis in TNBC cells. This, in turn, inhibits their viability and proliferation (172). Overall, cuproptosis plays a crucial role in predicting and treating breast cancer, holding significant value for exploring genetic detection methods and repurposing existing drugs for anticancer effects.

Importance of ferroptosis for breast cancer cells

In ferroptosis, the activation status is of the pathway is significantly associated with clinical outcomes and intra-tumor heterogeneity in breast cancer. The detection of NDUFA13 expression levels provides a means with which to infer this activation status (173). Notably, ferroptosis-related genes extend beyond predicting patient prognosis, also playing an immunologically active role in immunotherapy.

For example, compared with normal samples, tumor samples exhibit a significantly lower expression of the ferroptosis-related gene, HIC1. Notably, HIC1 expression varies across different clinical stages of breast cancer. Furthermore, HIC1 significantly participates in immune-related biological functions and signaling pathways, with its expression being directly associated with the response to PD-1/PD-L1 inhibitors in cancer therapy (174). Beyond enhancing the chemotherapeutic efficacy (as aforementioned), ferroptosis can also potentiate radiotherapy in breast cancer. Constructing tumor microenvironment-degradable nanohybrids that incorporate ferroptosis in a dual radiosensitization mode markedly improves therapeutic efficacy and anti-metastatic efficiency (175). Overall, ferroptosis is significantly associated with early breast cancer invasion and recurrence, highlighting its importance in treatment comprehensiveness and predictive accuracy. Not only are ferroptosis-related genes used for patient prognosis, but also channel proteins are being explored to further enhance prediction accuracy. Consequently, ferroptosis provides a multifaceted approach for the treatment of breast cancer, capable of augmenting the efficacy of both chemotherapy and radiotherapy.

Importance of pyroptosis for breast cancer cells

In cellular pyroptosis, certain lncRNAs associated with the pathway can predict the prognosis of patients with breast cancer. For instance, a higher expression of RP11-459E5.1 has been shown to be associated with a poorer overall survival, while high levels of RP11-1070N10.3 and RP11-817J15.3 are associated with an improved survival (176). Additionally, pyroptosis-related genes can even predict the potential target organs for breast cancer metastasis. The analysis of patients with TNBC and brain metastases has revealed significant differences in AIM2 and ZBP1 expression between primary tumors and metastases. Notably, a high AIM2 expression predictsa worse prognosis, while a high ZBP1 expression suggests improved outcomes, suggesting their potential as biomarkers for TNBC brain metastasis (177). Furthermore, chemotherapeutic agents capable of inducing pyroptosis have promising potential for use in the treatment of breast cancer. Derivatives, such as 3-acyl isoquinoline-1 (2H)-ones can trigger GSDME-mediated pyroptosis, leading to apoptosis and inhibiting the proliferation of breast cancer cells without harming normal breast cells (178). The unique advantage of pyroptosis lies in the ability of related genes to predict metastatic organs and the relative lack of toxicity of its associated drugs towards normal cells, both contributing to improved patient prognosis.

Across cuproptosis, ferroptosis and pyroptosis, various molecules can be used to predict the prognosis of patients with breast cancer. Additionally, targeting these pathways or their mechanisms through drug development presents opportunities to enhance treatment efficacy. All three types of RCD hold immense potential for future research and breast cancer treatment. While ferroptosis research currently boasts more applied and comprehensive studies, including prognostic prediction encompassing developmental stages, it is important to acknowledge the ongoing investigation and promise of cuproptosis and pyroptosis as well. Moreover, ferroptosis-related drugs may enhance not only chemotherapy, but also radiotherapy, potentially rendering it the first form of RCD to reach clinical application.

9. Conclusion and future perspectives

Breast cancer poses a significant threat to human life and health. Its growth, development and metastasis are intricately linked to the body's own gene regulation and immune defense mechanisms. RCD, an intrinsic component of these physiological programs, plays a crucial role in tumor regulation and defense. The academic community is steadily uncovering and proposing the regulatory mechanisms of cuproptosis, ferroptosis, pyroptosis and other forms of RCD in breast cancer. The development of novel drugs and ongoing clinical trials (presented in Table I) highlight the strong association between these pathways and breast cancer, offering a promising new direction for research. Several emerging drugs and clinical agents have demonstrated the ability to induce RCD in breast cancer cells. However, ongoing research is necessary to fully understand the potential mechanisms of RCD and further explore and test related drugs in clinical trials. By harnessing the power of RCD, it is hoped that future advancements in treatment can improve treatment efficacy, enhance the quality of life, and increase the survival rate of patients with breast cancer.

Table I

Utilization of scientifically and technologically constructed drugs related to regulated cell death.

Table I

Utilization of scientifically and technologically constructed drugs related to regulated cell death.

DrugTarget of action/mechanismRegulatory cell death involvedPotency(Refs.)
Type-I AIE photosensitizer loaded biomimetic systemLipoylated protein aggregation and iron-sulfur protein lossCuproptosisInhibits lung metastasis of breast cancer and prevents tumor rechallenge(61)
HD/BER/GOx/Cu hydrogel systemProduces starvation/chemodynamic therapy and induces copper deathCuproptosisPreoperative reduction of breast cancer size to facilitate surgical excision(62)
Heparanase-driven sequential released nanoparticlesEffectively enhances intracellular ROS levels and activates the iron death pathway. Enhanced ROS also induces the apoptotic pathway and reduces the expression of MMP-9FerroptosisNew dosage regimens for the treatment of breast cancer by intracellular and extracellular mechanisms(93)
Polydopamine nanoparticlesCombination with DOX induces ferroptosis in breast cancer cellsFerroptosisPossesses anti-tumor activity and selectivity, increasing the accuracy and effectiveness of targeted therapies(94)
Cinnamaldehyde dimersDepletion of glutathione, in combination with the anti-breast cancer drug sorafenib (sorafenib.SRF), resulted in a significant enhancement of iron death, and by promoting dendritic cell maturation and CD8+ T-cell initiationFerroptosisIncreasing the anticancer effects of sorafenib(95)
erastin@FA-exoInhibits the expression of GPX4 and upregulates the expression of CDO1FerroptosisMay reduce side effects in tumor therapy and may replace traditional erastin in clinical practice(96)
Biomimetic nanoparticle (BNP) loaded with indocyanine green (ICG) and decitabine (DCT)Induced cleavage of GSDMEPyroptosisControlled tumor growth and stimulated anticancer immune responses(139)
Carrier-free chemophotodynamic nanoplatformTriggering GSDME-Mediated ScorchDeath in a controlled manner via ROS accumulationPyroptosisComplement chemotherapy or immunotherapy for cancer metastasis(140)

[i] HD, hyaluronic acid-dopamine; BER, berberine hydrochloride; GOx, glucose oxidase; ROS, reactive oxygen species; DOX, doxorubicin; GSDME, gasdermin E.

Availability of data and materials

Not applicable.

Authors' contributions

LA, CQ, WH, KZ, QH, LJ and HL searched the literature for related studies for the review and prepared the manuscript and figures. LL and NY provided constructive guidance and made critical revisions. LA participated in the main editing of the manuscript. LA, CQ, LL and NY participated in the design of the review. All authors have read and approved the final manuscript. Data authentication is not applicable.

Ethics approval and consent to participate

Not applicable.

Patient consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.


Not applicable.


The present study was supported by the Xinjiang Uygur Autonomous Region Natural Science Foundation (Program no. 2023D01C40) and the National Natural Science Foundation of China (Program no. 81660459).



Xia C, Dong X, Li H, Cao M, Sun D, He S, Yang F, Yan X, Zhang S, Li N and Chen W: Cancer statistics in China and United States, 2022: Profiles, trends, and determinants. Chin Med J (Engl). 135:584–590. 2022. View Article : Google Scholar : PubMed/NCBI


Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI


Cameron D, Piccart-Gebhart MJ, Gelber RD, Procter M, Goldhirsch A, de Azambuja E, Castro G Jr, Untch M, Smith I, Gianni L, et al: 11 years' follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive early breast cancer: Final analysis of the HERceptin Adjuvant (HERA) trial. Lancet. 389:1195–1205. 2017. View Article : Google Scholar : PubMed/NCBI


Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I and Andrews DW: Molecular mechanisms of cell death: Recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 25:486–541. 2018. View Article : Google Scholar : PubMed/NCBI


Tang D, Kang R, Berghe TV, Vandenabeele P and Kroemer G: The molecular machinery of regulated cell death. Cell Res. 29:347–364. 2019. View Article : Google Scholar : PubMed/NCBI


Conradt B: Genetic control of programmed cell death during animal development. Annu Rev Genet. 43:493–523. 2009. View Article : Google Scholar : PubMed/NCBI


Fuchs Y and Steller H: Programmed cell death in animal development and disease. Cell. 147:742–758. 2011. View Article : Google Scholar : PubMed/NCBI


Galluzzi L, Bravo-San Pedro JM, Kepp O and Kroemer G: Regulated cell death and adaptive stress responses. Cell Mol Life Sci. 73:2405–2410. 2016. View Article : Google Scholar : PubMed/NCBI


Lutsenko S: Human copper homeostasis: A network of interconnected pathways. Curr Opin Chem Biol. 14:211–217. 2010. View Article : Google Scholar : PubMed/NCBI


Gaggelli E, Kozlowski H, Valensin D and Valensin G: Copper homeostasis and neurodegenerative disorders (Alzheimer's, prion, and Parkinson's diseases and amyotrophic lateral sclerosis). Chem Rev. 106:1995–2044. 2006. View Article : Google Scholar : PubMed/NCBI


Festa RA and Thiele DJ: Copper: An essential metal in biology. Curr Biol. 21:R877–R883. 2011. View Article : Google Scholar : PubMed/NCBI


Chillappagari S, Seubert A, Trip H, Kuipers OP, Marahiel MA and Miethke M: Copper stress affects iron homeostasis by destabilizing iron-sulfur cluster formation in Bacillus subtilis. J Bacteriol. 192:2512–2524. 2010. View Article : Google Scholar : PubMed/NCBI


Macomber L and Imlay JA: The iron-sulfur clusters of dehydratases are primary intracellular targets of copper toxicity. Proc Natl Acad Sci USA. 106:8344–8349. 2009. View Article : Google Scholar : PubMed/NCBI


Wang Y, Zhang L and Zhou F: Cuproptosis: A new form of programmed cell death. Cell Mol Immunol. 19:867–868. 2022. View Article : Google Scholar : PubMed/NCBI


Tang D, Chen X and Kroemer G: Cuproptosis: A coppertriggered modality of mitochondrial cell death. Cell Res. 32:417–418. 2022. View Article : Google Scholar : PubMed/NCBI


Tsvetkov P, Coy S, Petrova B, Dreishpoon M, Verma A, Abdusamad M, Rossen J, Joesch-Cohen L, Humeidi R, Spangler RD, et al: Copper induces cell death by targeting lipoylated TCA cycle proteins. Science. 375:1254–1261. 2022. View Article : Google Scholar : PubMed/NCBI


Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI


Tsvetkov P, Detappe A, Cai K, Keys HR, Brune Z, Ying W, Thiru P, Reidy M, Kugener G, Rossen J, et al: Mitochondrial metabolism promotes adaptation to proteotoxic stress. Nat Chem Biol. 15:681–689. 2019. View Article : Google Scholar : PubMed/NCBI


Skrott Z, Majera D, Gursky J, Buchtova T, Hajduch M, Mistrik M and Bartek J: Disulfiram's anti-cancer activity reflects targeting NPL4, not inhibition of aldehyde dehydrogenase. Oncogene. 38:6711–6722. 2019. View Article : Google Scholar : PubMed/NCBI


Pan M, Zheng Q, Yu Y, Ai H, Xie Y, Zeng X, Wang C, Liu L and Zhao M: Seesaw conformations of Npl4 in the human p97 complex and the inhibitory mechanism of a disulfiram derivative. Nat Commun. 12:1212021. View Article : Google Scholar : PubMed/NCBI


Tsang T, Posimo JM, Gudiel AA, Cicchini M, Feldser DM and Brady DC: Copper is an essential regulator of the autophagic kinases ULK1/2 to drive lung adenocarcinoma. Nat Cell Biol. 22:412–424. 2020. View Article : Google Scholar : PubMed/NCBI


Davis CI, Gu X, Kiefer RM, Ralle M, Gade TP and Brady DC: Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation. Metallomics. 12:1995–2008. 2020. View Article : Google Scholar : PubMed/NCBI


Ge EJ, Bush AI, Casini A, Cobine PA, Cross JR, DeNicola GM, Dou QP, Franz KJ, Gohil VM, Gupta S, et al: Connecting copper and cancer: From transition metal signalling to metalloplasia. Nat Rev Cancer. 22:102–113. 2022. View Article : Google Scholar :


Hasinoff BB, Yadav AA, Patel D and Wu X: The cytotoxicity of the anticancer drug elesclomol is due to oxidative stress indirectly mediated through its complex with Cu(II). J Inorg Biochem. 137:22–30. 2014. View Article : Google Scholar : PubMed/NCBI


Tardito S, Bassanetti I, Bignardi C, Elviri L, Tegoni M, Mucchino C, Bussolati O, Franchi-Gazzola R and Marchiò L: Copper binding agents acting as copper ionophores lead to caspase inhibition and paraptotic cell death in human cancer cells. J Am Chem Soc. 133:6235–6242. 2011. View Article : Google Scholar : PubMed/NCBI


Pavithra V, Sathisha TG, Kasturi K, Mallika DS, Amos SJ and Ragunatha S: Serum levels of metal ions in female patients with breast cancer. J Clin Diagn Res. 9:BC25–BC27. 2015.PubMed/NCBI


Wu J, Zhu Y, Luo M and Li L: Comprehensive analysis of pyroptosis-related genes and tumor microenvironment infiltration characterization in breast cancer. Front Immunol. 12:7482212021. View Article : Google Scholar : PubMed/NCBI


Brady DC, Crowe MS, Turski ML, Hobbs GA, Yao X, Chaikuad A, Knapp S, Xiao K, Campbell SL, Thiele DJ and Counter CM: Copper is required for oncogenic BRAF signalling and tumorigenesis. Nature. 509:492–496. 2014. View Article : Google Scholar : PubMed/NCBI


Cui L, Gouw AM, LaGory EL, Guo S, Attarwala N, Tang Y, Qi J, Chen YS, Gao Z, Casey KM, et al: Mitochondrial copper depletion suppresses triple-negative breast cancer in mice. Nat Biotechnol. 39:357–367. 2021. View Article : Google Scholar


Blockhuys S, Zhang X and Wittung-Stafshede P: Single-cell tracking demonstrates copper chaperone Atox1 to be required for breast cancer cell migration. Proc Natl Acad Sci USA. 117:2014–2019. 2020. View Article : Google Scholar : PubMed/NCBI


Kirshner JR, He S, Balasubramanyam V, Kepros J, Yang CY, Zhang M, Du Z, Barsoum J and Bertin J: Elesclomol induces cancer cell apoptosis through oxidative stress. Mol Cancer Ther. 7:2319–2327. 2008. View Article : Google Scholar : PubMed/NCBI


Nagai M, Vo NH, Shin Ogawa L, Chimmanamada D, Inoue T, Chu J, Beaudette-Zlatanova BC, Lu R, Blackman RK, Barsoum J, et al: The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells. Free Radic Biol Med. 52:2142–2150. 2012. View Article : Google Scholar : PubMed/NCBI


Yadav AA, Patel D, Wu X and Hasinoff BB: Molecular mechanisms of the biological activity of the anticancer drug elesclomol and its complexes with Cu(II), Ni(II) and Pt(II). J Inorg Biochem. 126:1–6. 2013. View Article : Google Scholar : PubMed/NCBI


Renier N, Reinaud O, Jabin I and Valkenier H: Transmembrane transport of copper(i) by imidazole-functionalised calix[4] arenes. Chem Commun (Camb). 56:8206–8209. 2020. View Article : Google Scholar : PubMed/NCBI


Chen L, Min J and Wang F: Copper homeostasis and cuproptosis in health and disease. Signal Transduct Target Ther. 7:3782022. View Article : Google Scholar : PubMed/NCBI


Smirnova J, Kabin E, Järving I, Bragina O, Tõugu V, Plitz T and Palumaa P: Copper(I)-binding properties of de-coppering drugs for the treatment of Wilson disease. α-Lipoic acid as a potential anti-copper agent. Sci Rep. 8:14632018. View Article : Google Scholar


He K, Chen Z, Ma Y and Pan Y: Identification of high-copper-responsive target pathways in Atp7b knockout mouse liver by GSEA on microarray data sets. Mamm Genome. 22:703–713. 2011. View Article : Google Scholar : PubMed/NCBI


Sheftel AD, Stehling O, Pierik AJ, Elsässer HP, Mühlenhoff U, Webert H, Hobler A, Hannemann F, Bernhardt R and Lill R: Humans possess two mitochondrial ferredoxins, Fdx1 and Fdx2, with distinct roles in steroidogenesis, heme, and Fe/S cluster biosynthesis. Proc Natl Acad Sci USA. 107:11775–11780. 2010. View Article : Google Scholar : PubMed/NCBI


Strushkevich N, MacKenzie F, Cherkesova T, Grabovec I, Usanov S and Park HW: Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system. Proc Natl Acad Sci USA. 108:10139–10143. 2011. View Article : Google Scholar : PubMed/NCBI


Zalewski A, Ma NS, Legeza B, Renthal N, Flück CE and Pandey AV: Vitamin D-Dependent rickets type 1 caused by mutations in CYP27B1 affecting protein interactions with adrenodoxin. J Clin Endocrinol Metab. 101:3409–3418. 2016. View Article : Google Scholar : PubMed/NCBI


Moriya M, Ho YH, Grana A, Nguyen L, Alvarez A, Jamil R, Ackland ML, Michalczyk A, Hamer P, Ramos D, et al: Copper is taken up efficiently from albumin and alpha2-macroglobulin by cultured human cells by more than one mechanism. Am J Physiol Cell Physiol. 295:C708–C721. 2008. View Article : Google Scholar : PubMed/NCBI


Xie J, Yang Y, Gao Y and He J: Cuproptosis: Mechanisms and links with cancers. Mol Cancer. 22:462023. View Article : Google Scholar : PubMed/NCBI


Lu Z and Hunter T: Metabolic kinases moonlighting as protein kinases. Trends Biochem Sci. 43:301–310. 2018. View Article : Google Scholar : PubMed/NCBI


Zhang L, Li M, Cui Z, Chai D, Guan Y, Chen C and Wang W: Systematic analysis of the role of SLC52A2 in multiple human cancers. Cancer Cell Int. 22:82022. View Article : Google Scholar : PubMed/NCBI


Halestrap AP: The SLC16 gene family-structure, role and regulation in health and disease. Mol Aspects Med. 34:337–349. 2013. View Article : Google Scholar : PubMed/NCBI


Higuchi K, Sugiyama K, Tomabechi R, Kishimoto H and Inoue K: Mammalian monocarboxylate transporter 7 (MCT7/Slc16a6) is a novel facilitative taurine transporter. J Biol Chem. 298:1018002022. View Article : Google Scholar : PubMed/NCBI


Wright ME, Peters U, Gunter MJ, Moore SC, Lawson KA, Yeager M, Weinstein SJ, Snyder K, Virtamo J and Albanes D: Association of variants in two vitamin e transport genes with circulating vitamin e concentrations and prostate cancer risk. Cancer Res. 69:1429–1438. 2009. View Article : Google Scholar : PubMed/NCBI


Tanaka T, Bai Z, Srinoulprasert Y, Yang BG, Hayasaka H and Miyasaka M: Chemokines in tumor progression and metastasis. Cancer Sci. 96:317–322. 2005. View Article : Google Scholar : PubMed/NCBI


de Marco MC, Martín-Belmonte F, Kremer L, Albar JP, Correas I, Vaerman JP, Marazuela M, Byrne JA and Alonso MA: MAL2, a novel raft protein of the MAL family, is an essential component of the machinery for transcytosis in hepatoma HepG2 cells. J Cell Biol. 159:37–44. 2002. View Article : Google Scholar : PubMed/NCBI


Li DD, Yagüe E, Wang LY, Dai LL, Yang ZB, Zhi S, Zhang N, Zhao XM and Hu YH: Novel copper complexes that inhibit the proteasome and trigger apoptosis in triple-negative breast cancer cells. ACS Med Chem Lett. 10:1328–1335. 2019. View Article : Google Scholar : PubMed/NCBI


Lee ZY, Leong CH, Lim KUL, Wong CCS, Pongtheerawan P, Arikrishnan SA, Tan KL, Loh JS, Low ML, How CW, et al: Induction of apoptosis and autophagy by ternary copper complex towards breast cancer cells. Anticancer Agents Med Chem. 22:1159–1170. 2022. View Article : Google Scholar


Li X, Ma Z and Mei L: Cuproptosis-related gene SLC31A1 is a potential predictor for diagnosis, prognosis and therapeutic response of breast cancer. Am J Cancer Res. 12:3561–3580. 2022.PubMed/NCBI


Li L, Li L and Sun Q: High expression of cuproptosis-related SLC31A1 gene in relation to unfavorable outcome and deregulated immune cell infiltration in breast cancer: An analysis based on public databases. BMC Bioinformatics. 23:3502022. View Article : Google Scholar : PubMed/NCBI


Li Z, Zhang H, Wang X, Wang Q, Xue J, Shi Y, Wang M, Wang G and Zhang J: Identification of cuproptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in breast cancer. Front Immunol. 13:9968362022. View Article : Google Scholar : PubMed/NCBI


Sha S, Si L, Wu X, Chen Y, Xiong H, Xu Y, Liu W, Mei H, Wang T and Li M: Prognostic analysis of cuproptosis-related gene in triple-negative breast cancer. Front Immunol. 13:9227802022. View Article : Google Scholar : PubMed/NCBI


Guan X, Lu N and Zhang J: Construction of a prognostic model related to copper dependence in breast cancer by single-cell sequencing analysis. Front Genet. 13:9498522022. View Article : Google Scholar : PubMed/NCBI


Jiang ZR, Yang LH, Jin LZ, Yi LM, Bing PP, Zhou J and Yang JS: Identification of novel cuproptosis-related lncRNA signatures to predict the prognosis and immune microenvironment of breast cancer patients. Front Oncol. 12:9886802022. View Article : Google Scholar : PubMed/NCBI


Zhao Q and Qi T: The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression. Front Oncol. 13:11171642023. View Article : Google Scholar : PubMed/NCBI


Song S, Zhang M, Xie P, Wang S and Wang Y: Comprehensive analysis of cuproptosis-related genes and tumor microenvironment infiltration characterization in breast cancer. Front Immunol. 13:9789092022. View Article : Google Scholar : PubMed/NCBI


Ning S, Lyu M, Zhu D, Lam JWY, Huang Q, Zhang T and Tang BZ: Type-I AIE photosensitizer loaded biomimetic system boosting cuproptosis to inhibit breast cancer metastasis and rechallenge. ACS Nano. 17:10206–10217. 2023. View Article : Google Scholar : PubMed/NCBI


Lee SY, Seo JH, Kim S, Hwang C, Jeong DI, Park J, Yang M, Huh JW and Cho HJ: Cuproptosis-Inducible chemotherapeutic/cascade catalytic reactor system for combating with breast cancer. Small. 19:e23014022023. View Article : Google Scholar : PubMed/NCBI


Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012. View Article : Google Scholar : PubMed/NCBI


Xu T, Ding W, Ji X, Ao X, Liu Y, Yu W and Wang J: Molecular mechanisms of ferroptosis and its role in cancer therapy. J Cell Mol Med. 23:4900–4912. 2019. View Article : Google Scholar : PubMed/NCBI


Gao M, Monian P, Quadri N, Ramasamy R and Jiang X: Glutaminolysis and transferrin regulate ferroptosis. Mol Cell. 59:298–308. 2015. View Article : Google Scholar : PubMed/NCBI


Lu B, Chen XB, Ying MD, He QJ, Cao J and Yang B: The role of ferroptosis in cancer development and treatment response. Front Pharmacol. 8:9922018. View Article : Google Scholar : PubMed/NCBI


Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, Fulda S, Gascón S, Hatzios SK, Kagan VE, et al: Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 171:273–285. 2017. View Article : Google Scholar : PubMed/NCBI


Xie Y, Wang B, Zhao Y, Tao Z, Wang Y, Chen G and Hu X: Mammary adipocytes protect triple-negative breast cancer cells from ferroptosis. J Hematol Oncol. 15:722022. View Article : Google Scholar : PubMed/NCBI


Wang YY, Attané C, Milhas D, Dirat B, Dauvillier S, Guerard A, Gilhodes J, Lazar I, Alet N, Laurent V, et al: Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight. 2:e874892017. View Article : Google Scholar : PubMed/NCBI


Yang D, Li Y, Xing L, Tan Y, Sun J, Zeng B, Xiang T, Tan J, Ren G and Wang Y: Utilization of adipocyte-derived lipids and enhanced intracellular trafficking of fatty acids contribute to breast cancer progression. Cell Commun Signal. 16:322018. View Article : Google Scholar : PubMed/NCBI


Liu W, Chakraborty B, Safi R, Kazmin D, Chang CY and McDonnell DP: Dysregulated cholesterol homeostasis results in resistance to ferroptosis increasing tumorigenicity and metastasis in cancer. Nat Commun. 12:51032021. View Article : Google Scholar : PubMed/NCBI


Baek AE, Yu YA, He S, Wardell SE, Chang CY, Kwon S, Pillai RV, McDowell HB, Thompson JW, Dubois LG, et al: The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells. Nat Commun. 8:8642017. View Article : Google Scholar : PubMed/NCBI


Vallianou NG, Kostantinou A, Kougias M and Kazazis C: Statins and cancer. Anticancer Agents Med Chem. 14:706–712. 2014. View Article : Google Scholar


Sha R, Xu Y, Yuan C, Sheng X, Wu Z, Peng J, Wang Y, Lin Y, Zhou L, Xu S, et al: Predictive and prognostic impact of ferroptosis-related genes ACSL4 and GPX4 on breast cancer treated with neoadjuvant chemotherapy. EBioMedicine. 71:1035602021. View Article : Google Scholar : PubMed/NCBI


Ding Y, Chen X, Liu C, Ge W, Wang Q, Hao X, Wang M, Chen Y and Zhang Q: Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells. J Hematol Oncol. 14:192021. View Article : Google Scholar


Zhang K, Ping L, Du T, Liang G, Huang Y, Li Z, Deng R and Tang J: A Ferroptosis-Related lncRNAs signature predicts prognosis and immune microenvironment for breast cancer. Front Mol Biosci. 8:6788772021. View Article : Google Scholar : PubMed/NCBI


Ping L, Zhang K, Ou X, Qiu X and Xiao X: A novel pyroptosis-associated long Non-coding RNA signature predicts prognosis and tumor immune microenvironment of patients with breast cancer. Front Cell Dev Biol. 9:7271832021. View Article : Google Scholar : PubMed/NCBI


Zhu Z and Leung GKK: More than a metabolic enzyme: MTHFD2 as a novel target for anticancer therapy? Front Oncol. 10:6582020. View Article : Google Scholar : PubMed/NCBI


Zhang H, Zhu S, Zhou H, Li R, Xia X and Xiong H: Identification of MTHFD2 as a prognostic biomarker and ferroptosis regulator in triple-negative breast cancer. Front Oncol. 13:10983572023. View Article : Google Scholar : PubMed/NCBI


Yadav P, Sharma P, Sundaram S, Venkatraman G, Bera AK and Karunagaran D: SLC7A11/xCT is a target of miR-5096 and its restoration partially rescues miR-5096-mediated ferroptosis and anti-tumor effects in human breast cancer cells. Cancer Lett. 522:211–224. 2021. View Article : Google Scholar : PubMed/NCBI


Koppula P, Zhuang L and Gan B: Cystine transporter SLC7A11/xCT in cancer: Ferroptosis, nutrient dependency, and cancer therapy. Protein Cell. 12:599–620. 2021. View Article : Google Scholar :


He J, Wang X, Chen K, Zhang M and Wang J: The amino acid transporter SLC7A11-mediated crosstalk implicated in cancer therapy and the tumor microenvironment. Biochem Pharmacol. 205:1152412022. View Article : Google Scholar : PubMed/NCBI


Zhang Y, Liang Y, Wang Y, Ye F, Kong X and Yang Q: A novel ferroptosis-related gene signature for overall survival prediction and immune infiltration in patients with breast cancer. Int J Oncol. 61:1482022. View Article : Google Scholar :


Liu Q, Ma JY and Wu G: Identification and validation of a ferroptosis-related gene signature predictive of prognosis in breast cancer. Aging (Albany NY). 13:21385–21399. 2021. View Article : Google Scholar : PubMed/NCBI


Xu Y, Du Y, Zheng Q, Zhou T, Ye B, Wu Y, Xu Q and Meng X: Identification of ferroptosis-related prognostic signature and subtypes related to the immune microenvironment for breast cancer patients receiving neoadjuvant chemotherapy. Front Immunol. 13:8951102022. View Article : Google Scholar : PubMed/NCBI


Yang YF, Lee YC, Wang YY, Wang CH, Hou MF and Yuan SF: YWHAE promotes proliferation, metastasis, and chemoresistance in breast cancer cells. Kaohsiung J Med Sci. 35:408–416. 2019. View Article : Google Scholar : PubMed/NCBI


Qiao X, Zhang Y, Sun L, Ma Q, Yang J, Ai L, Xue J, Chen G, Zhang H, Ji C, et al: Association of human breast cancer CD44-/CD24-cells with delayed distant metastasis. Elife. 10:e654182021. View Article : Google Scholar


Gong Z, Li Q, Shi J, Liu ET, Shultz LD and Ren G: Lipid-laden lung mesenchymal cells foster breast cancer metastasis via metabolic reprogramming of tumor cells and natural killer cells. Cell Metab. 34:1960–1976.e9. 2022. View Article : Google Scholar : PubMed/NCBI


Li Y, Jin K, van Pelt GW, van Dam H, Yu X, Mesker WE, Ten Dijke P, Zhou F and Zhang L: c-Myb enhances breast cancer invasion and metastasis through the Wnt/β-Catenin/Axin2 pathway. Cancer Res. 76:3364–3375. 2016. View Article : Google Scholar : PubMed/NCBI


Li Y, Zhang Y, Liu X, Wang M, Wang P, Yang J and Zhang S: Lutein inhibits proliferation, invasion and migration of hypoxic breast cancer cells via downregulation of HES1. Int J Oncol. 52:2119–2129. 2018.PubMed/NCBI


Huo Q, Wang J and Xie N: High HSPB1 expression predicts poor clinical outcomes and correlates with breast cancer metastasis. BMC Cancer. 23:5012023. View Article : Google Scholar : PubMed/NCBI


Zhang H, Ge Z, Wang Z, Gao Y, Wang Y and Qu X: Circular RNA RHOT1 promotes progression and inhibits ferroptosis via mir-106a-5p/STAT3 axis in breast cancer. Aging (Albany NY). 13:8115–8126. 2021. View Article : Google Scholar : PubMed/NCBI


Zhou Y, Che Y, Fu Z, Zhang H and Wu H: Triple-Negative breast cancer analysis based on metabolic gene classification and immunotherapy. Front Public Health. 10:9023782022. View Article : Google Scholar : PubMed/NCBI


Zhang J, Yang J, Zuo T, Ma S, Xokrat N, Hu Z, Wang Z, Xu R, Wei Y and Shen Q: Heparanase-driven sequential released nanoparticles for ferroptosis and tumor microenvironment modulations synergism in breast cancer therapy. Biomaterials. 266:1204292021. View Article : Google Scholar


Nieto C, Vega MA and Martín Del Valle EM: Tailored-Made polydopamine nanoparticles to induce ferroptosis in breast cancer cells in combination with chemotherapy. Int J Mol Sci. 22:31612021. View Article : Google Scholar : PubMed/NCBI


Zhou Z, Liang H, Yang R, Yang Y, Dong J, Di Y and Sun M: Glutathione depletion-induced activation of dimersomes for potentiating the ferroptosis and immunotherapy of 'cold' tumor. Angew Chem Int Ed Engl. 61:e2022028432022. View Article : Google Scholar


Dattachoudhury S, Sharma R, Kumar A and Jaganathan BG: Sorafenib inhibits proliferation, migration and invasion of breast cancer cells. Oncology. 98:478–486. 2020. View Article : Google Scholar : PubMed/NCBI


Yu M, Gai C, Li Z, Ding D, Zheng J, Zhang W, Lv S and Li W: Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Sci. 110:3173–3182. 2019. View Article : Google Scholar : PubMed/NCBI


Yang J, Zhou Y, Xie S, Wang J, Li Z, Chen L, Mao M, Chen C, Huang A, Chen Y, et al: Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer. J Exp Clin Cancer Res. 40:2062021. View Article : Google Scholar : PubMed/NCBI


Ma S, Henson ES, Chen Y and Gibson SB: Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis. 7:e23072016. View Article : Google Scholar : PubMed/NCBI


Ma S, Dielschneider RF, Henson ES, Xiao W, Choquette TR, Blankstein AR, Chen Y and Gibson SB: Ferroptosis and autophagy induced cell death occur independently after siramesine and lapatinib treatment in breast cancer cells. PLoS One. 12:e01829212017. View Article : Google Scholar : PubMed/NCBI


Chen Z, Li R, Fang M, Wang Y, Bi A, Yang L, Song T, Li Y, Li Q, Lin B, et al: Integrated analysis of FKBP1A/SLC3A2 axis in everolimus inducing ferroptosis of breast cancer and anti-proliferation of T lymphocyte. Int J Med Sci. 20:1060–1078. 2023. View Article : Google Scholar : PubMed/NCBI


Li H, Liu W, Zhang X, Wu F, Sun D and Wang Z: Ketamine suppresses proliferation and induces ferroptosis and apoptosis of breast cancer cells by targeting KAT5/GPX4 axis. Biochem Biophys Res Commun. 585:111–116. 2021. View Article : Google Scholar : PubMed/NCBI


Song X, Wang X, Liu Z and Yu Z: Role of GPX4-Mediated ferroptosis in the sensitivity of triple negative breast cancer cells to gefitinib. Front Oncol. 10:5974342020. View Article : Google Scholar


Yao X, Xie R, Cao Y, Tang J, Men Y, Peng H and Yang W: Simvastatin induced ferroptosis for triple-negative breast cancer therapy. J Nanobiotechnology. 19:3112021. View Article : Google Scholar : PubMed/NCBI


Zhang Z, Lu M, Chen C, Tong X, Li Y, Yang K, Lv H, Xu J and Qin L: Holo-lactoferrin: the link between ferroptosis and radiotherapy in triple-negative breast cancer. Theranostics. 11:3167–3182. 2021. View Article : Google Scholar : PubMed/NCBI


Sun D, Li YC and Zhang XY: Lidocaine promoted ferroptosis by targeting miR-382-5p/SLC7A11 axis in ovarian and breast cancer. Front Pharmacol. 12:6812232021. View Article : Google Scholar


Li R, Zhang J, Zhou Y, Gao Q, Wang R, Fu Y, Zheng L and Yu H: Transcriptome Investigation and in vitro verification of curcumin-induced HO-1 as a feature of ferroptosis in breast cancer cells. Oxid Med Cell Longev. 2020:34698402020. View Article : Google Scholar : PubMed/NCBI


Zhai FG, Liang QC, Wu YY, Liu JQ and Liu JW: Red ginseng polysaccharide exhibits anticancer activity through GPX4 downregulation-induced ferroptosis. Pharm Biol. 60:909–914. 2022. View Article : Google Scholar : PubMed/NCBI


Cookson BT and Brennan MA: Pro-inflammatory programmed cell death. Trends Microbiol. 9:113–114. 2001. View Article : Google Scholar : PubMed/NCBI


Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F and Shao F: Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526:660–665. 2015. View Article : Google Scholar : PubMed/NCBI


Järveläinen HA, Galmiche A and Zychlinsky A: Caspase-1 activation by Salmonella. Trends Cell Biol. 13:204–209. 2003. View Article : Google Scholar : PubMed/NCBI


Martinon F, Burns K and Tschopp J: The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 10:417–426. 2002. View Article : Google Scholar : PubMed/NCBI


Feng S, Fox D and Man SM: Mechanisms of gasdermin family members in inflammasome signaling and cell death. J Mol Biol. 430(18 Pt B): 3068–3080. 2018. View Article : Google Scholar : PubMed/NCBI


Shi J, Zhao Y, Wang Y, Gao W, Ding J, Li P, Hu L and Shao F: Inflammatory caspases are innate immune receptors for intracellular LPS. Nature. 514:187–192. 2014. View Article : Google Scholar : PubMed/NCBI


Xia J, Chu C, Li W, Chen H, Xie W, Cheng R, Hu K and Li X: Mitochondrial Protein UCP1 inhibits the malignant behaviors of triple-negative breast cancer through activation of mitophagy and pyroptosis. Int J Biol Sci. 18:2949–2961. 2022. View Article : Google Scholar : PubMed/NCBI


Yu X, Shi M, Wu Q, Wei W, Sun S and Zhu S: Identification of UCP1 and UCP2 as potential prognostic markers in breast cancer: A study based on immunohistochemical analysis and bioinformatics. Front Cell Dev Biol. 10:8917312022. View Article : Google Scholar : PubMed/NCBI


Zhang Z, Zhang Y, Xia S, Kong Q, Li S, Liu X, Junqueira C, Meza-Sosa KF, Mok TMY, Ansara J, et al: Gasdermin E suppresses tumour growth by activating anti-tumour immunity. Nature. 579:415–420. 2020. View Article : Google Scholar : PubMed/NCBI


Yi M, Niu M, Xu L, Luo S and Wu K: Regulation of PD-L1 expression in the tumor microenvironment. J Hematol Oncol. 14:102021. View Article : Google Scholar : PubMed/NCBI


Zhang M, Wu K, Wang M, Bai F and Chen H: CASP9 as a prognostic biomarker and promising drug target plays a pivotal role in inflammatory breast cancer. Int J Anal Chem. 2022:10434452022. View Article : Google Scholar : PubMed/NCBI


Chu L, Yi Q, Yan Y, Peng J, Li Z, Jiang F, He Q, Ouyang L, Wu S, Fu C, et al: A prognostic signature consisting of pyroptosis-related genes and SCAF11 for predicting immune response in breast cancer. Front Med (Lausanne). 9:8827632022. View Article : Google Scholar : PubMed/NCBI


Xu D, Ji Z and Qiang L: Molecular characteristics, clinical implication, and cancer immunity interactions of pyroptosis-related genes in breast cancer. Front Med (Lausanne). 8:7026382021. View Article : Google Scholar : PubMed/NCBI


Zhou Y, Zheng J, Bai M, Gao Y and Lin N: Effect of pyroptosis-related genes on the prognosis of breast cancer. Front Oncol. 12:9481692022. View Article : Google Scholar : PubMed/NCBI


Jin H and Kim HJ: NLRC4, ASC and Caspase-1 are inflammasome components that are mediated by P2Y2R activation in breast cancer cells. Int J Mol Sci. 21:33372020. View Article : Google Scholar :


Hergueta-Redondo M, Sarrió D, Molina-Crespo Á, Megias D, Mota A, Rojo-Sebastian A, García-Sanz P, Morales S, Abril S, Cano A, et al: Gasdermin-B promotes invasion and metastasis in breast cancer cells. PLoS One. 9:e900992014. View Article : Google Scholar : PubMed/NCBI


Song C, Kendi AT, Lowe VJ and Lee S: The A20/TNFAIP3-CDC20-CASP1 axis promotes inflammation-mediated metastatic disease in triple-negative breast cancer. Anticancer Res. 42:681–695. 2022. View Article : Google Scholar : PubMed/NCBI


Velloso FJ, Campos AR, Sogayar MC and Correa RG: Proteome profiling of triple negative breast cancer cells overexpressing NOD1 and NOD2 receptors unveils molecular signatures of malignant cell proliferation. BMC Genomics. 20:1522019. View Article : Google Scholar : PubMed/NCBI


Miao H, Wang L, Zhan H, Dai J, Chang Y, Wu F, Liu T, Liu Z, Gao C, Li L and Song X: A long noncoding RNA distributed in both nucleus and cytoplasm operates in the PYCARD-regulated apoptosis by coordinating the epigenetic and translational regulation. PLoS Genet. 15:e10081442019. View Article : Google Scholar : PubMed/NCBI


Faria SS, Costantini S, de Lima VCC, de Andrade VP, Rialland M, Cedric R, Budillon A and Magalhães KG: NLRP3 inflammasome-mediated cytokine production and pyroptosis cell death in breast cancer. J Biomed Sci. 28:262021. View Article : Google Scholar : PubMed/NCBI


Siersbæk R, Scabia V, Nagarajan S, Chernukhin I, Papachristou EK, Broome R, Johnston SJ, Joosten SEP, Green AR, Kumar S, et al: IL6/STAT3 signaling hijacks estrogen receptor α enhancers to drive breast cancer metastasis. Cancer Cell. 38:412–423.e9. 2020. View Article : Google Scholar


Wei Y, Huang H, Qiu Z, Li H, Tan J, Ren G and Wang X: NLRP1 overexpression is correlated with the tumorigenesis and proliferation of human breast tumor. Biomed Res Int. 2017:49384732017. View Article : Google Scholar : PubMed/NCBI


Tan Y, Sun R, Liu L, Yang D, Xiang Q, Li L, Tang J, Qiu Z, Peng W, Wang Y, et al: Tumor suppressor DRD2 facilitates M1 macrophages and restricts NF-κB signaling to trigger pyroptosis in breast cancer. Theranostics. 11:5214–5231. 2021. View Article : Google Scholar :


Zhang Z, Zhang H, Li D, Zhou X, Qin Q and Zhang Q: Caspase-3-mediated GSDME induced Pyroptosis in breast cancer cells through the ROS/JNK signalling pathway. J Cell Mol Med. 25:8159–8168. 2021. View Article : Google Scholar : PubMed/NCBI


An H, Heo JS, Kim P, Lian Z, Lee S, Park J, Hong E, Pang K, Park Y, Ooshima A, et al: Tetraarsenic hexoxide enhances generation of mitochondrial ROS to promote pyroptosis by inducing the activation of caspase-3/GSDME in triple-negative breast cancer cells. Cell Death Dis. 12:1592021. View Article : Google Scholar : PubMed/NCBI


Ma JH, Qin L and Li X: Role of STAT3 signaling pathway in breast cancer. Cell Commun Signal. 18:332020. View Article : Google Scholar : PubMed/NCBI


Wu L, Bai S, Huang J, Cui G, Li Q, Wang J, Du X, Fu W, Li C, Wei W, et al: Nigericin boosts anti-tumor immune response via inducing pyroptosis in triple-negative breast cancer. Cancers (Basel). 15:32212023. View Article : Google Scholar : PubMed/NCBI


Wang H, Rong X, Zhao G, Zhou Y, Xiao Y, Ma D, Jin X, Wu Y, Yan Y, Yang H, et al: The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer. Cell Metab. 34:581–594.e8. 2022. View Article : Google Scholar : PubMed/NCBI


Lei S, Li S, Xiao W, Jiang Q, Yan S, Xiao W, Cai J, Wang J, Zou L, Chen F, et al: Azurocidin 1 inhibits the aberrant proliferation of triple-negative breast cancer through the regulation of pyroptosis. Oncol Rep. 50:1882023. View Article : Google Scholar


Pizato N, Luzete BC, Kiffer LFMV, Corrêa LH, de Oliveira Santos I, Assumpção JAF, Ito MK and Magalhães KG: Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells. Sci Rep. 8:19522018. View Article : Google Scholar : PubMed/NCBI


Chen C, Yuan S, Chen X, Xie J and Wei Z: Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway. Am J Cancer Res. 13:1347–1362. 2023.PubMed/NCBI


Li Y, Wang W, Li A, Huang W, Chen S, Han F and Wang L: Dihydroartemisinin induces pyroptosis by promoting the AIM2/caspase-3/DFNA5 axis in breast cancer cells. Chem Biol Interact. 340:1094342021. View Article : Google Scholar : PubMed/NCBI


Zhong C, Li Y, Li W, Lian S, Li Y, Wu C, Zhang K, Zhou G, Wang W, Xu H, et al: Ganoderma lucidum extract promotes tumor cell pyroptosis and inhibits metastasis in breast cancer. Food Chem Toxicol. 174:1136542023. View Article : Google Scholar : PubMed/NCBI


Zhao P, Wang M, Chen M, Chen Z, Peng X, Zhou F, Song J and Qu J: Programming cell pyroptosis with biomimetic nanoparticles for solid tumor immunotherapy. Biomaterials. 254:1201422020. View Article : Google Scholar : PubMed/NCBI


Li L, Tian H, Zhang Z, Ding N, He K, Lu S, Liu R, Wu P, Wang Y, He B, et al: Carrier-Free nanoplatform via evoking pyroptosis and immune response against breast cancer. ACS Appl Mater Interfaces. 15:452–468. 2023. View Article : Google Scholar


Li C, Wang X, Chen T, Li W, Zhou X, Wang L and Yang Q: Huaier induces immunogenic cell death via CircCLASP1/PKR/eIF2α signaling pathway in triple negative breast cancer. Front Cell Dev Biol. 10:9138242022. View Article : Google Scholar


Yamamoto A, Huang Y, Krajina BA, McBirney M, Doak AE, Qu S, Wang CL, Haffner MC and Cheung KJ: Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7. Proc Natl Acad Sci USA. 120:e22148881202023. View Article : Google Scholar : PubMed/NCBI


Wen N, Lv Q and Du ZG: MicroRNAs involved in drug resistance of breast cancer by regulating autophagy. J Zhejiang Univ Sci B. 21:690–702. 2020. View Article : Google Scholar : PubMed/NCBI


Wu Q and Sharma D: Autophagy and breast cancer: connected in growth, progression, and therapy. Cells. 12:11562023. View Article : Google Scholar : PubMed/NCBI


Tadokoro T, Ikeda M, Ide T, Deguchi H, Ikeda S, Okabe K, Ishikita A, Matsushima S, Koumura T, Yamada KI, et al: Mitochondria-dependent ferroptosis plays a pivotal role in doxorubicin cardiotoxicity. JCI Insight. 8:e1697562023. View Article : Google Scholar : PubMed/NCBI


Wang Y, Shi P, Chen Q, Huang Z, Zou D, Zhang J, Gao X and Lin Z: Mitochondrial ROS promote macrophage pyroptosis by inducing GSDMD oxidation. J Mol Cell Biol. 11:1069–1082. 2019. View Article : Google Scholar : PubMed/NCBI


Dai S, Chen Y, Fan X, Han J, Zhong L, Zhang Y, Liu Q, Lin J, Huang W, Su L, et al: Emodin attenuates cardiomyocyte pyroptosis in doxorubicin-induced cardiotoxicity by directly binding to GSDMD. Phytomedicine. 121:1551052023. View Article : Google Scholar : PubMed/NCBI


Lu S, Tian H, Li B, Li L, Jiang H, Gao Y, Zheng L, Huang C, Zhou Y, Du Z and Xu J: An ellagic acid coordinated copper-based nanoplatform for efficiently overcoming cancer chemoresistance by cuproptosis and synergistic inhibition of cancer cell stemness. Small. Dec 3–2023.Epub ahead of print.


Zhong Y, Peng Z, Peng Y, Li B, Pan Y, Ouyang Q, Sakiyama H, Muddassir M and Liu J: Construction of Fe-doped ZIF-8/DOX nanocomposites for ferroptosis strategy in the treatment of breast cancer. J Mater Chem B. 11:6335–6345. 2023. View Article : Google Scholar : PubMed/NCBI


Wang J, Li Y, Zhang J and Luo C: Isoliquiritin modulates ferroptosis via NF-κB signaling inhibition and alleviates doxorubicin resistance in breast cancer. Immunopharmacol Immunotoxicol. 45:443–454. 2023. View Article : Google Scholar : PubMed/NCBI


Yu R, Wang L, Ji X and Mao C: SBP-0636457, a novel smac mimetic, cooperates with doxorubicin to induce necroptosis in breast cancer cells during apoptosis blockage. J Oncol. 2022:23900782022. View Article : Google Scholar : PubMed/NCBI


Wei T, Xiaojun X and Peilong C: Magnoflorine improves sensitivity to doxorubicin (DOX) of breast cancer cells via inducing apoptosis and autophagy through AKT/mTOR and p38 signaling pathways. Biomed Pharmacother. 121:1091392020. View Article : Google Scholar


Lu Y, Pan Q, Gao W, Pu Y and He B: Reversal of cisplatin chemotherapy resistance by glutathione-resistant copper-based nanomedicine via cuproptosis. J Mater Chem B. 10:6296–6306. 2022. View Article : Google Scholar : PubMed/NCBI


Roh JL, Kim EH, Jang HJ, Park JY and Shin D: Induction of ferroptotic cell death for overcoming cisplatin resistance of head and neck cancer. Cancer Lett. 381:96–103. 2016. View Article : Google Scholar : PubMed/NCBI


Wang Y, Pang X, Liu Y, Mu G and Wang Q: SOCS1 acts as a ferroptosis driver to inhibit the progression and chemotherapy resistance of triple-negative breast cancer. Carcinogenesis. 44:708–715. 2023. View Article : Google Scholar : PubMed/NCBI


Zhang X, Sui S, Wang L, Li H, Zhang L, Xu S and Zheng X: Inhibition of tumor propellant glutathione peroxidase 4 induces ferroptosis in cancer cells and enhances anticancer effect of cisplatin. J Cell Physiol. 235:3425–3437. 2020. View Article : Google Scholar


Yan H, Luo B, Wu X, Guan F, Yu X, Zhao L, Ke X, Wu J and Yuan J: Cisplatin induces pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in triple-negative breast cancer. Int J Biol Sci. 17:2606–2621. 2021. View Article : Google Scholar : PubMed/NCBI


Shen M, Duan WM, Wu MY, Wang WJ, Liu L, Xu MD, Zhu J, Li DM, Gui Q, Lian L, et al: Participation of autophagy in the cytotoxicity against breast cancer cells by cisplatin. Oncol Rep. 34:359–367. 2015. View Article : Google Scholar : PubMed/NCBI


Peng F, Liao M, Qin R, Zhu S, Peng C, Fu L, Chen Y and Han B: Regulated cell death (RCD) in cancer: Key pathways and targeted therapies. Signal Transduct Target Ther. 7:2862022. View Article : Google Scholar : PubMed/NCBI


Li J, Cao F, Yin HL, Huang ZJ, Lin ZT, Mao N, Sun B and Wang G: Ferroptosis: Past, present and future. Cell Death Dis. 11:882020. View Article : Google Scholar : PubMed/NCBI


Shi J, Gao W and Shao F: Pyroptosis: Gasdermin-Mediated programmed necrotic cell death. Trends Biochem Sci. 42:245–254. 2017. View Article : Google Scholar


Song L, Zeng R, Yang K, Liu W, Xu Z and Kang F: The biological significance of cuproptosis-key gene MTF1 in pan-cancer and its inhibitory effects on ROS-mediated cell death of liver hepatocellular carcinoma. Discov Oncol. 14:1132023. View Article : Google Scholar : PubMed/NCBI


Zheng D, Liu J, Piao H, Zhu Z, Wei R and Liu K: ROS-triggered endothelial cell death mechanisms: Focus on pyroptosis, parthanatos, and ferroptosis. Front Immunol. 13:10392412022. View Article : Google Scholar : PubMed/NCBI


Abais JM, Xia M, Zhang Y, Boini KM and Li PL: Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Signal. 22:1111–1129. 2015. View Article : Google Scholar :


Li C and Zhang Y: Construction and validation of a cuproptosis-related five-lncRNA signature for predicting prognosis, immune response and drug sensitivity in breast cancer. BMC Med Genomics. 16:1582023. View Article : Google Scholar : PubMed/NCBI


Xu Z, Wang X, Sun W, Xu F, Kou H, Hu W, Zhang Y, Jiang Q, Tang J and Xu Y: RelB-activated GPX4 inhibits ferroptosis and confers tamoxifen resistance in breast cancer. Redox Biol. 68:1029522023. View Article : Google Scholar : PubMed/NCBI


Xu W, Song C, Wang X, Li Y, Bai X, Liang X, Wu J and Liu J: Downregulation of miR-155-5p enhances the anti-tumor effect of cetuximab on triple-negative breast cancer cells via inducing cell apoptosis and pyroptosis. Aging (Albany NY). 13:228–240. 2021. View Article : Google Scholar : PubMed/NCBI


Shen Y, Li D, Liang Q, Yang M, Pan Y and Li H: Cross-talk between cuproptosis and ferroptosis regulators defines the tumor microenvironment for the prediction of prognosis and therapies in lung adenocarcinoma. Front Immunol. 13:10290922022. View Article : Google Scholar


Yang X, Deng L, Diao X, Yang S, Zou L, Yang Q, Li J, Nie J, Zhao L and Jiao B: Targeting cuproptosis by zinc pyrithione in triple-negative breast cancer. iScience. 26:1082182023. View Article : Google Scholar : PubMed/NCBI


Li Y, Li T, Zhai D, Xie C, Kuang X, Lin Y and Shao N: Quantification of ferroptosis pathway status revealed heterogeneity in breast cancer patients with distinct immune microenvironment. Front Oncol. 12:9569992022. View Article : Google Scholar : PubMed/NCBI


Wu Y, Lin Z, Tang X, Tong Z, Ji Y, Xu Y, Zhou Z, Yang J, Li Z and Liu T: Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity. Front Immunol. 14:11820302023. View Article : Google Scholar : PubMed/NCBI


Zeng L, Ding S, Cao Y, Li C, Zhao B, Ma Z, Zhou J, Hu Y, Zhang X, Yang Y, et al: A MOF-Based potent ferroptosis inducer for enhanced radiotherapy of triple negative breast cancer. ACS Nano. 17:13195–13210. 2023. View Article : Google Scholar : PubMed/NCBI


Yang X, Weng X, Yang Y and Jiang Z: Pyroptosis-Related lncRNAs predict the prognosis and immune response in patients with breast cancer. Front Genet. 12:7921062021. View Article : Google Scholar


Huang QF, Fang DL, Nong BB and Zeng J: Focal pyroptosis-related genes AIM2 and ZBP1 are prognostic markers for triple-negative breast cancer with brain metastases. Transl Cancer Res. 10:4845–4858. 2021. View Article : Google Scholar


Ma L, Bian M, Gao H, Zhou Z and Yi W: A novel 3-acyl isoquinolin-1(2H)-one induces G2 phase arrest, apoptosis and GSDME-dependent pyroptosis in breast cancer. PLoS One. 17:e02680602022. View Article : Google Scholar : PubMed/NCBI

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Volume 64 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Ai L, Yi N, Qiu C, Huang W, Zhang K, Hou Q, Jia L, Li H and Liu L: Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review). Int J Oncol 64: 46, 2024
Ai, L., Yi, N., Qiu, C., Huang, W., Zhang, K., Hou, Q. ... Liu, L. (2024). Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review). International Journal of Oncology, 64, 46.
Ai, L., Yi, N., Qiu, C., Huang, W., Zhang, K., Hou, Q., Jia, L., Li, H., Liu, L."Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)". International Journal of Oncology 64.5 (2024): 46.
Ai, L., Yi, N., Qiu, C., Huang, W., Zhang, K., Hou, Q., Jia, L., Li, H., Liu, L."Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review)". International Journal of Oncology 64, no. 5 (2024): 46.