Lung cancer refers to tumors originating from the lung parenchyma (1). It is the most common cancer globally, both in terms of incidence and mortality. In total, ~2 million individuals are diagnosed with lung cancer annually, leading to ~1.8 million deaths (2). The mortality rate from lung cancer exceeds the combined deaths caused by prostate, breast, brain and colorectal cancers (3). Small-cell lung cancer (SCLC) accounts for 15% of all cases, while non-small cell lung cancer (NSCLC) comprises 85%, marking the two primary subtypes of the disease (4). NSCLC, in particular, is the most extensively studied form of cancer, with the highest number of publications recorded in 2022(5). Epidemiological data indicate that the general population experiences a lung cancer incidence rate of 69 per 100,000 individuals, with this rate increasing substantially to 751 per 100,000 men over the age of 75. This increase is primarily attributed to both advanced age and the higher prevalence of lung cancer among males (6).

Effective management planning for lung cancer requires determining the tumor, lymph node and metastasis (TNM) staging, as treatment strategies are based on the cancer's stage and the extent of metastasis (7-9). Surgical intervention is an option for patients with resectable NSCLC in stages I, II and IIIA (10). In addition to surgery, the treatment of NSCLC includes radiotherapy, chemotherapy, immunotherapy and targeted molecular therapy. Targeted therapy, a relatively new treatment approach, continues to evolve as researchers identify new biological targets (7). Among the targeted therapies, dasatinib, an FDA-approved multi-kinase inhibitor, is primarily utilized for the treatment of chronic myeloid leukemia. Additionally, it demonstrates significant antiproliferative effects on various solid tumors, particularly when used in combination with other therapeutic agents, including those for prostate, breast, lung and pancreatic cancers (11).

The present meta-analysis evaluates the efficacy of dasatinib, both as monotherapy and in combination with other therapies, in the management of lung cancer. All references have been checked to exclude any non-peer-reviewed data (12).

Cancer continues to pose a significant societal, public health, and economic challenge in the 21st century, accounting for nearly one in six deaths globally (16.8%) and one in four deaths (22.8%) attributed to non-communicable diseases (NCDs) (22). Traditionally viewed primarily as a genetic disease, this perspective fails to address complex clinical phenomena such as recurrence and drug resistance. Recent advancements suggest a more integrative framework, characterizing cancer as a ‘multidimensional spatiotemporal unity of ecology and evolution’, a dynamic pathological ecosystem which cancer cells interact with their microenvironment and undergo evolutionary changes over time. This paradigm offers critical insights into cancer progression, providing novel strategies to tackle clinical challenges such as therapeutic resistance and disease relapse (23). The disease accounts for 30.3% of premature deaths due to NCDs among individuals aged 30-69 years, ranking as one of the top three causes of death within this age group across 177 of 183 countries (22). For lung cancer specifically, exposure to cigarette smoke, radiation, asbestos, and metals such as nickel, chromium and arsenic significantly elevates risk (2). Smoking remains the primary cause, accounting for ~85% of all lung cancer cases (24). In the present study, 39 (16.7%) out of the 234 patients reported a history of smoking.

Lung cancer is broadly categorized into two primary types: SCLC and NSCLC (25). Within NSCLC, adenocarcinoma, squamous cell carcinoma and large cell carcinoma represent the major histological subtypes, with adenocarcinoma constituting 40%, squamous cell carcinoma 25-30% and large cell carcinoma 5-10% (5). The findings of the present study revealed that adenocarcinoma was present in 118 patients (63.8%), while squamous cell carcinoma was identified in 41 patients (22.1%). Sex distribution patterns also vary across studies. A study conducted by Ruano-Ravina et al indicated that among 13,950 participants, 25.6% were female, with female participants tending to be younger, while smoking prevalence was higher among males (26). By contrast, the current study found no significant sex disparity, with males comprising 51.7% and female 48.3% of the cohort.

Sehgal et al (27) conducted a study on patients with advanced-stage NSCLC undergoing treatment with pembrolizumab, demonstrating that those with an ECOG performance status of 2 or higher had significantly lower disease control rates, shorter median overall survival and reduced PFS. These findings underscore the critical importance of baseline ECOG status as a determinant of treatment effectiveness and patient outcomes. In the present study, the majority of patients had an ECOG status of one (58.1%), with fewer patients having a status of zero (29.1%) or two (2.1%).

Treatment strategies for lung cancer are according to the tumors' characteristics and stage of progression. Options include immunotherapy, chemotherapy, radiotherapy, molecular targeted therapy and surgical intervention. Surgical resection with curative intent is typically reserved for patients with early TNM stages (I or II) who are in sufficient overall health to endure the procedure (28,29). Despite transformative advancements in molecular targeted therapy and immuno-oncology, chemotherapy continues to serve as a cornerstone of lung cancer management. Studies consistently demonstrate its positive effect on both survival and quality of life, spanning early and advanced disease stages, whether administered as a monotherapy or in combination with other treatments. Moreover, emerging combination regimens and innovative drug delivery systems hold significant promise for enhancing treatment efficacy (30).

Radiotherapy plays a critical role in managing stage III NSCLC, though its effectiveness depends on the extent of the disease. For Pancoast tumors, a treatment regimen combining induction chemo-radiotherapy followed by surgery has demonstrated improved survival rates. However, in resectable N2-NSCLC, neoadjuvant chemoradiotherapy does not provide a survival benefit over chemotherapy alone. Postoperative radiotherapy does not generally improve outcomes in completely resected N2 disease, except in cases with positive margins. Concurrent chemoradiotherapy, often supplemented by durvalumab, remains the standard approach for unresectable N2 or N3 NSCLC. Advanced techniques such as intensity-modulated radiation therapy can mitigate the risk of severe pneumonitis; though their overall effectiveness varies. For patients at higher risk, radiotherapy alone may provide a modest survival benefit (31). Targeted therapy has emerged as a crucial strategy for treating NSCLC, based on the understanding that multiple oncogenic mutations drive lung cancer development. Identifying these specific genetic alterations enables the development of targeted therapies to directly combat these mutations (32). Beyond NSCLC, targeted therapies have also shown efficacy in treating other cancers, with pembrolizumab and durvalumab demonstrating effectiveness in mesothelioma (33,34).

Dasatinib inhibits cell proliferation and survival while inducing apoptosis in hematologic malignancies and solid tumors. At a concentration of 10 µM, it reduces viability and induces apoptosis in HSC-3 cells. Additionally, it significantly inhibits the proliferation and survival of YD-8, YD-10B, HSC-3 and YD-38 cells, with YD-38 cells being the most sensitive, underscoring its broad effectiveness across various cell lines (35). Johnson et al (13) conducted a phase II trial evaluating dasatinib in advanced NSCLC. Patients received dasatinib as first-line therapy, with response assessments performed via CT and PET imaging. Pre-treatment tissue samples were analyzed for EGFR and KRAS mutations as well as expression of phosphorylated Src family kinases (SFK). Among 34 patients, the disease control rate was 43%, with one partial response and a metabolic response rate of 32%. Notably, EGFR and KRAS mutations did not predict treatment response (13). In the aforementioned study, 56 patients (52.4%) in the dasatinib-alone group exhibited progressive disease, 24 patients (22.4%) had stable disease, one patient (0.9%) had a partial response, and the response status of 26 patients (24.3%) was unknown. Several factors could account for these outcomes. One possibility is the inherent aggressiveness of the lung cancer in these patients, particularly in those with advanced stages of the disease. Dasatinib, though effective in some malignancies, may have limited efficacy as a monotherapy in specific lung cancer subtypes without actionable mutations (for example, EGFR or KRAS), which could partially explain the limited disease control observed. Another potential explanation is treatment-induced hyper-progression, where certain therapies, including tyrosine kinase inhibitors and immune checkpoint inhibitors, accelerate tumour growth in a subset of patients. While dasatinib has demonstrated efficacy in hematologic malignancies and certain solid tumors, it may induce hyper-progression in a minority of patients with lung cancer, leading to higher rates of progression (36). Further researches are needed to clarify the role of hyper-progression in dasatinib-treated patients with lung cancer, particularly concerning specific genetic profiles or pre-existing conditions.

Dasatinib has also been evaluated with other therapies such as osimertinib, afatinib and other targeted therapies. Haura et al (14) conducted a phase I trial involving group A combination therapy, where patients with advanced NSCLC received erlotinib for one week before dasatinib was introduced. Pharmacokinetics were assessed at weeks 1 and 2, across four dasatinib dosage cohorts. Adverse events included gastrointestinal issues, skin rash, cytopenia, pleural effusions and fatigue. The study reported two partial responses and one bone response, with a disease control rate of 63%. Additionally, plasma angiogenic markers decreased during treatment, correlating with disease control. This combination therapy was tolerable and demonstrated potential efficacy in NSCLC, warranting further exploration of personalized SFK-targeting strategies (14). In the present study, 127 patients (54.3%) underwent combination therapies, while 107 patients (45.7%) received dasatinib alone. In group A, 31 patients (38.3%) achieved stable disease, 24 patients (29.6%) experienced progression, and seven patients (8.6%) exhibited a partial response. The response status of the remaining 19 patients (23.5%) was unspecified.

The utilization of dasatinib in lung cancer treatment remains a topic of ongoing debate within the oncology community. While dasatinib is primarily approved for chronic myeloid leukemia and acute lymphoblastic leukemia with BCR-ABL positivity, its off-label use in various solid tumors, including lung cancer, raises important questions regarding efficacy and safety. Studies have indicated that dasatinib exhibits significant antiproliferative effects against a range of malignancies, particularly when used in conjunction with other therapeutic agents. These effects are largely attributed to its inhibition of SFKs, which induces cytotoxicity and apoptosis in tumor cells (11). Despite these promising findings, the lack of large-scale clinical trials specifically assessing effectiveness of dasatinib in lung cancer necessitates caution. Challenges such as the potential for drug resistance and the need for personalized treatment strategies highlight the complexities of its off-label use. As ongoing research continues to explore the therapeutic potential of dasatinib in various malignancies, a nuanced understanding of its role in lung cancer is essential to guide clinical decision-making and optimize patient outcomes.

Dasatinib is generally well tolerated, with adverse events that are typically manageable and often occur early in the course of treatment. These events are often mild to moderate, resolving either spontaneously, with supportive care, or through temporary treatment interruption or dose adjustments. Effective management of adverse events is crucial for ensuring treatment adherence and optimizing therapeutic outcomes. Adverse events are categorized using common terminology criteria, with the most frequent being cytopenia, fluid retention, pleural effusion, dyspnea, gastrointestinal problems, skin rash, headache and fatigue (34). In the current study, anemia was the most common hematological adverse event, affecting 57 patients (42.2%). The incidence of anemia was particularly higher in the combination therapy group, with 41 cases (50.6%) reported in group A, compared with only 4 cases (3.7%) in the dasatinib monotherapy group. Diarrhea was also a significant adverse event within the gastrointestinal group, affecting 86 patients (35.4%) overall. It was especially prevalent in the group A combination therapy cohort, where 59 patients (72.8%) experienced diarrhea, compared with only 3 cases (2.8%) in the dasatinib monotherapy group, 8 cases (80.0%) in group B, and 15 cases (60.0%) in the group C. Dermatological adverse events were also common, with skin rash reported in 80 cases (85.1%). Group A demonstrated the highest incidence, with 57 cases (70.4%), compared with 3 cases (2.8%) in the monotherapy group, 7 cases (70.0%) in group B, and 13 cases (52.0%) in group C.

In addition to the limitation of including only one published article on the role of dasatinib in lung cancer over the last five years, other limitations of the study include the small sample size, with only nine eligible studies included in the meta-analysis, which may reduce the generalizability of the findings. Additionally, significant heterogeneity across studies, particularly in the combination therapy group, complicates the interpretation of results and suggests variability in treatment protocols.

In conclusion, dasatinib treatment may improve overall survival and have fewer adverse events compared with combination therapies in patients with lung cancer. The present study holds significant practical implications by advancing the understanding and potential applications of targeted therapies such as dasatinib in lung cancer management. By systematically evaluating its efficacy and safety as a standalone treatment, current findings can inform clinical decision-making and optimize treatment strategies to improve patient outcomes. Furthermore, the present research highlights the need for large-scale trials to validate these findings, which could pave the way for more personalized and effective therapeutic approaches in oncology. If confirmed, the standalone use of dasatinib could offer a streamlined treatment option, reducing the complexity and adverse effects associated with combination therapies, thereby improving patient quality of life. The present study represents a critical step in expanding therapeutic options and guiding future research in this vital area of medicine.