Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
December-2025 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2025 Volume 30 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Role of signaling pathways in lung cancer development and advances in targeted therapies (Review)

  • Authors:
    • Zhang Tao
    • Weiwei Shao
    • Haiyang Zhou
    • Shujing Xia
    • Jie Zeng
    • Jing Ren
    • Xueyang Wang
    • Hua Zhu
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China, Department of Pathology, Yancheng No. 1 People's Hospital, Yancheng, Jiangsu 224000, P.R. China, Department of Gastroenterology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China, Department of Imaging, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224001, P.R. China, Department of Gastroenterology, Yancheng Third People's Hospital, Yancheng, Jiangsu 224001, P.R. China
    Copyright: © Tao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 589
    |
    Published online on: October 14, 2025
       https://doi.org/10.3892/ol.2025.15335
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Lung cancer is one of the most prevalent and lethal cancers worldwide, markedly contributing to cancer‑related morbidity and mortality. The development and progression of lung cancer involve intricate signaling pathways that regulate essential cellular processes such as proliferation, survival, metastasis and resistance to therapy. These pathways can be disrupted by genetic mutations, epigenetic alterations or environmental factors including tobacco smoke and air pollution. In the past decade, considerable advancements have been made in elucidating the molecular mechanisms underlying lung cancer pathogenesis. This progress has facilitated the identification of key oncogenic drivers and the development of targeted therapies that have revolutionized treatment options. The present review provides an overview of critical signaling pathways implicated in lung cancer pathogenesis, including EGFR, anaplastic lymphoma kinase, KRAS, PI3K/AKT/mTOR and immune checkpoints. It also examines recent developments in targeted therapies such as next‑generation tyrosine kinase inhibitors, monoclonal antibodies and combination strategies along with their clinical implications. By highlighting the molecular complexities associated with lung cancer and emerging therapeutic innovations, the present review highlights the significance of precision medicine in improving patient outcomes and shaping future treatments for lung cancer.
View Figures

Figure 1

Role of EGFR signaling in the
development of lung cancer. (A) The EGFR pathway serves a central
role in the pathogenesis of NSCLC. Mutations within the EGFR kinase
domain, such as exon 19 deletions, L858R and T790M, markedly
increase EGFR kinase activity. (B) This hyperactivation
subsequently initiates a cascade of downstream signaling pathways,
including MAPK, PI3K/Akt/mTOR and IL-6/JAK/STAT3, all of which
contribute to tumorigenesis in NSCLC cells. EGFR, epidermal growth
factor receptor; NSCLC, non-small cell lung cancer; MAPK,
mitogen-activated protein kinases; PI3K, phosphoinositide 3-kinase,
Akt, protein kinase B; mTOR, mammalian target of rapamycin; IL-6,
interleukin-6; JAK, janus kinase; STAT3, signal transducer and
activator of transcription 3.

Figure 2

EML4-ALK fusion and its signaling
network. (A) Schematic diagram illustrating the fusion between the
N-terminal portion of EML4, which includes its basic region, the
HELP domain, part of the WD-repeat region and the intracellular
domain of ALK containing the tyrosine kinase domain. Notable, the
TM domain is missing in the final fusion protein. (B) As a
constitutively active tyrosine kinase, the EML4-ALK fusion protein
activates multiple key signaling pathways involved in promoting
cell proliferation, survival and metastasis. EML4, echinoderm
microtubule-associated protein-like 4; ALK, anaplastic lymphoma
kinase; TM, transmembrane.

Figure 3

The KRAS protein is a critical GTPase
that regulates cell proliferation, survival and differentiation
through multiple signaling pathways, including the MAPK/ERK and
PI3K/AKT cascades. KRAS, kirsten rat sarcoma; GTPase, guanosine
triphosphatases; MAPK, mitogen-activated protein kinases; ERK,
extracellular regulated protein kinases; PI3K, phosphoinositide
3-kinase; AKT, protein kinase B.

Figure 4

Schematic illustration of the
PI3K/Akt/mTOR signaling pathway. The activation of the PI3K pathway
is initiated by the binding of a ligand to a receptor tyrosine
kinase, which results in the release of p110α (the catalytic
subunit) from p85 (the regulatory subunit). Alternatively, this
pathway can also be activated through GPCR signaling. Once
activated, p110α catalyzes the conversion of PIP2 into PIP3.
Following PIP3 production, this lipid second messenger can either
directly activate Akt or assist in the recruitment of PDK1.
Thereafter, both PDK1 and mTORC1 contribute to phosphorylate and
activate Akt. Upon activation, Akt stimulates cell growth by
modulating the mTOR complex and its downstream effector S6K.
Moreover, Akt inhibits FOXO1 and activates NF-κB, thereby
suppressing apoptosis. Additionally, Akt promotes MDM2 activity,
which subsequently suppresses p53 function. By contrast, PTEN
antagonizes PIP3-mediated signaling, thus restraining processes
such as cell survival, growth and proliferation. PI3K,
phosphoinositide 3-kinase; Akt, protein kinase B; mTOR, mammalian
target of rapamycin; GPCR, G protein-coupled receptors; PIP,
phosphatidylinositol(4,5)bisphosphate; PDK1, 3-phosphoinositide
dependent protein kinase-1; mTORC1, mechanistic target of rapamycin
complex 1; FOXO1, forkhead box other 1; NF-κB, nuclear factor κB;
MDM2, mouse double minute 2; PTEN, phosphatase and tensin
homolog.

Figure 5

Costimulatory pathways in T cell
activation. The activation of T cells is tightly regulated through
the interactions of multiple costimulatory molecules. Stimulatory
signals are provided by the binding of CD27 to CD70, OX40 to OX40L,
4-1BB to 4-1BBL, and CD28 to B7 ligands, whilst inhibitory signals
are mediated by the PD-1/PD-L1 and CTLA-4/B7 interactions. OX40L,
OX40 ligand; 4-1BBL, 4-1BB ligand; PD-1, programmed death-1; PD-L1,
programmed death-1 ligand.
View References

1 

Li Y, Wu X, Yang P, Jiang G and Luo Y: Machine learning for lung cancer diagnosis, treatment, and prognosis. Genomics Proteomics Bioinformatics. 20:850–866. 2022. View Article : Google Scholar : PubMed/NCBI

2 

Bade BC and Dela Cruz CS: Lung cancer 2020: Epidemiology, etiology, and prevention. Clin Chest Med. 41:1–24. 2020. View Article : Google Scholar : PubMed/NCBI

3 

Harðardottir H, Jonsson S, Gunnarsson O, Hilmarsdottir B, Asmundsson J, Gudmundsdottir I, Saevarsdottir VY, Hansdottir S, Hannesson P and Gudbjartsson T: Advances in lung cancer diagnosis and treatment-a review. Laeknabladid. 108:17–29. 2020.(In Icelandic). View Article : Google Scholar

4 

Abu Rous F, Singhi EK, Sridhar A, Faisal MS and Desai A: Lung cancer treatment advances in 2022. Cancer Invest. 41:12–24. 2023. View Article : Google Scholar : PubMed/NCBI

5 

Wu F, Wang L and Zhou C: Lung cancer in China: Current and prospect. Curr Opin Oncol. 33:40–46. 2021. View Article : Google Scholar : PubMed/NCBI

6 

Rodriguez-Canales J, Parra-Cuentas E and Wistuba II: Diagnosis and molecular classification of lung cancer. Cancer Treat Res. 170:25–46. 2016. View Article : Google Scholar : PubMed/NCBI

7 

de Sousa VML and Carvalho L: Heterogeneity in lung cancer. Pathobiology. 85:96–107. 2018. View Article : Google Scholar : PubMed/NCBI

8 

Abolfathi H, Arabi M and Sheikhpour M: A literature review of microRNA and gene signaling pathways involved in the apoptosis pathway of lung cancer. Respir Res. 24:552023. View Article : Google Scholar : PubMed/NCBI

9 

Niu Z, Jin R, Zhang Y and Li H: Signaling pathways and targeted therapies in lung squamous cell carcinoma: Mechanisms and clinical trials. Signal Transduct Target Ther. 7:3532022. View Article : Google Scholar : PubMed/NCBI

10 

Yuan M, Zhao Y, Arkenau HT, Lao T, Chu L and Xu Q: Signal pathways and precision therapy of small-cell lung cancer. Signal Transduct Target Ther. 7:1872022. View Article : Google Scholar : PubMed/NCBI

11 

Masciale V, Banchelli F, Grisendi G, Samarelli AV, Raineri G, Rossi T, Zanoni M, Cortesi M, Bandini S, Ulivi P, et al: The molecular features of lung cancer stem cells in dedifferentiation process-driven epigenetic alterations. J Biol Chem. 300:1079942024. View Article : Google Scholar : PubMed/NCBI

12 

Hoque MO, Brait M, Rosenbaum E, Poeta ML, Pal P, Begum S, Dasgupta S, Carvalho AL, Ahrendt SA, Westra WH and Sidransky D: Genetic and epigenetic analysis of erbB signaling pathway genes in lung cancer. J Thorac Oncol. 5:1887–1893. 2010. View Article : Google Scholar : PubMed/NCBI

13 

He H, He MM, Wang H, Qiu W, Liu L, Long L, Shen Q, Zhang S, Qin S, Lu Z, et al: In utero and childhood/adolescence exposure to tobacco smoke, genetic risk, and lung cancer incidence and mortality in adulthood. Am J Respir Crit Care Med. 207:173–182. 2023. View Article : Google Scholar : PubMed/NCBI

14 

Chen CY, Huang KY, Chen CC, Chang YH, Li HJ, Wang TH and Yang PC: The role of PM2.5 exposure in lung cancer: Mechanisms, genetic factors, and clinical implications. EMBO Mol Med. 17:31–40. 2025. View Article : Google Scholar : PubMed/NCBI

15 

Nagano T, Tachihara M and Nishimura Y: Molecular mechanisms and targeted therapies including immunotherapy for non-small cell lung cancer. Curr Cancer Drug Targets. 19:595–630. 2019. View Article : Google Scholar : PubMed/NCBI

16 

Samarelli AV, Masciale V, Aramini B, Coló GP, Tonelli R, Marchioni A, Bruzzi G, Gozzi F, Andrisani D, Castaniere I, et al: Molecular mechanisms and cellular contribution from lung fibrosis to lung cancer development. Int J Mol Sci. 22:121792021. View Article : Google Scholar : PubMed/NCBI

17 

Ohmori T, Yamaoka T, Ando K, Kusumoto S, Kishino Y, Manabe R and Sagara H: Molecular and clinical features of EGFR-TKI-associated lung injury. Int J Mol Sci. 22:7922021. View Article : Google Scholar : PubMed/NCBI

18 

Schneider JL, Lin JJ and Shaw AT: ALK-positive lung cancer: A moving target. Nat Cancer. 4:330–343. 2023. View Article : Google Scholar : PubMed/NCBI

19 

Reck M, Carbone DP, Garassino M and Barlesi F: Targeting KRAS in non-small-cell lung cancer: Recent progress and new approaches. Ann Oncol. 32:1101–1110. 2021. View Article : Google Scholar : PubMed/NCBI

20 

Yoda S, Dagogo-Jack I and Hata AN: Targeting oncogenic drivers in lung cancer: Recent progress, current challenges and future opportunities. Pharmacol Ther. 193:20–30. 2019. View Article : Google Scholar : PubMed/NCBI

21 

Herrera-Juárez M, Serrano-Gómez C, Bote-de-Cabo H and Paz-Ares L: Targeted therapy for lung cancer: Beyond EGFR and ALK. Cancer. 129:1803–1820. 2023. View Article : Google Scholar : PubMed/NCBI

22 

Yoneda K, Imanishi N, Ichiki Y and Tanaka F: Treatment of non-small cell lung cancer with EGFR-mutations. J UOEH. 41:153–163. 2019. View Article : Google Scholar : PubMed/NCBI

23 

Hosomi Y, Morita S, Sugawara S, Kato T, Fukuhara T, Gemma A, Takahashi K, Fujita Y, Harada T, Minato K, et al: Gefitinib alone versus gefitinib plus chemotherapy for non-small-cell lung cancer with mutated epidermal growth factor receptor: NEJ009 study. J Clin Oncol. 38:115–123. 2020. View Article : Google Scholar : PubMed/NCBI

24 

Greenhalgh J, Bagust A, Boland A, Dwan K, Beale S, Hockenhull J, Proudlove C, Dundar Y, Richardson M, Dickson R, et al: Erlotinib and gefitinib for treating non-small cell lung cancer that has progressed following prior chemotherapy (review of NICE technology appraisals 162 and 175): A systematic review and economic evaluation. Health Technol Assess. 19:1–134. 2015. View Article : Google Scholar

25 

Remon J, Besse B, Aix SP, Callejo A, Al-Rabi K, Bernabe R, Greillier L, Majem M, Reguart N, Monnet I, et al: Osimertinib treatment based on plasma T790M monitoring in patients with EGFR-mutant non-small-cell lung cancer (NSCLC): EORTC lung cancer group 1613 APPLE phase II randomized clinical trial. Ann Oncol. 34:468–476. 2023. View Article : Google Scholar : PubMed/NCBI

26 

Abdelgalil AA and Alkahtani HM: Crizotinib: A comprehensive profile. Profiles Drug Subst Excip Relat Methodol. 48:39–69. 2023. View Article : Google Scholar : PubMed/NCBI

27 

Peters S, Camidge DR, Shaw AT, Gadgeel S, Ahn JS, Kim DW, Ou SI, Pérol M, Dziadziuszko R, Rosell R, et al: Alectinib versus crizotinib in untreated ALK-positive non-small-cell lung cancer. N Engl J Med. 377:829–838. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Solomon BJ, Liu G, Felip E, Mok TSK, Soo RA, Mazieres J, Shaw AT, de Marinis F, Goto Y, Wu YL, et al: Lorlatinib versus crizotinib in patients with advanced ALK-positive non-small cell lung cancer: 5-Year outcomes from the phase III CROWN study. J Clin Oncol. 42:3400–3409. 2024. View Article : Google Scholar : PubMed/NCBI

29 

Luo J, Ostrem J, Pellini B, Imbody D, Stern Y, Solanki HS, Haura EB and Villaruz LC: Overcoming KRAS-mutant lung cancer. Am Soc Clin Oncol Educ Book. 42:1–11. 2022.PubMed/NCBI

30 

Jänne PA, Riely GJ, Gadgeel SM, Heist RS, Ou SI, Pacheco JM, Johnson ML, Sabari JK, Leventakos K, Yau E, et al: Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation. N Engl J Med. 387:120–131. 2022. View Article : Google Scholar : PubMed/NCBI

31 

Skoulidis F, Li BT, Dy GK, Price TJ, Falchook GS, Wolf J, Italiano A, Schuler M, Borghaei H, Barlesi F, et al: Sotorasib for lung cancers with KRAS p.G12C mutation. N Engl J Med. 384:2371–2381. 2021. View Article : Google Scholar : PubMed/NCBI

32 

Olivier T and Prasad V: Sotorasib in KRAS(G12C) mutated lung cancer. Lancet. 403:1452024. View Article : Google Scholar : PubMed/NCBI

33 

Sanaei MJ, Razi S, Pourbagheri-Sigaroodi A and Bashash D: The PI3K/Akt/mTOR pathway in lung cancer; oncogenic alterations, therapeutic opportunities, challenges, and a glance at the application of nanoparticles. Transl Oncol. 18:1013642022. View Article : Google Scholar : PubMed/NCBI

34 

Iksen, Pothongsrisit S and Pongrakhananon V: Targeting the PI3K/AKT/mTOR signaling pathway in lung cancer: An update regarding potential drugs and natural products. Molecules. 26:41002021. View Article : Google Scholar : PubMed/NCBI

35 

Ghareghomi S, Atabaki V, Abdollahzadeh N, Ahmadian S and Hafez Ghoran S: Bioactive PI3-kinase/Akt/mTOR inhibitors in targeted lung cancer therapy. Adv Pharm Bull. 13:24–35. 2023.PubMed/NCBI

36 

Tan AC: Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer (NSCLC). Thorac Cancer. 11:511–518. 2020. View Article : Google Scholar : PubMed/NCBI

37 

Chen B, Song Y, Zhan Y, Zhou S, Ke J, Ao W, Zhang Y, Liang Q, He M, Li S, et al: Fangchinoline inhibits non-small cell lung cancer metastasis by reversing epithelial-mesenchymal transition and suppressing the cytosolic ROS-related Akt-mTOR signaling pathway. Cancer Lett. 543:2157832022. View Article : Google Scholar : PubMed/NCBI

38 

Li J, Zhang D, Wang S, Yu P, Sun J, Zhang Y, Meng X, Li J and Xiang L: Baicalein induces apoptosis by inhibiting the glutamine-mTOR metabolic pathway in lung cancer. J Adv Res. 68:341–357. 2025. View Article : Google Scholar : PubMed/NCBI

39 

Cheng W, Kang K, Zhao A and Wu Y: Dual blockade immunotherapy targeting PD-1/PD-L1 and CTLA-4 in lung cancer. J Hematol Oncol. 17:542024. View Article : Google Scholar : PubMed/NCBI

40 

Shen X, Huang S, Xiao H, Zeng S, Liu J, Ran Z and Xiong B: Efficacy and safety of PD-1/PD-L1 plus CTLA-4 antibodies ± other therapies in lung cancer: A systematic review and meta-analysis. Eur J Hosp Pharm. 30:3–8. 2023. View Article : Google Scholar : PubMed/NCBI

41 

Vergnenegre A and Chouaid C: Economic analyses of immune-checkpoint inhibitors to treat lung cancer. Expert Rev Pharmacoecon Outcomes Res. 21:365–371. 2021. View Article : Google Scholar : PubMed/NCBI

42 

Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, et al: Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 372:2018–2028. 2015. View Article : Google Scholar : PubMed/NCBI

43 

Cascone T, Awad MM, Spicer JD, He J, Lu S, Sepesi B, Tanaka F, Taube JM, Cornelissen R, Havel L, et al: Perioperative nivolumab in resectable lung cancer. N Engl J Med. 390:1756–1769. 2024. View Article : Google Scholar : PubMed/NCBI

44 

Felip E, Altorki N, Zhou C, Vallières E, Martínez-Martí A, Rittmeyer A, Chella A, Reck M, Goloborodko O, Huang M, et al: Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II–IIIA non-small-cell lung cancer (IMpower010): A randomised, multicentre, open-label, phase III trial. Ann Oncol. 34:907–919. 2023. View Article : Google Scholar : PubMed/NCBI

45 

Zhang T, Li W, Diwu D, Chen L, Chen X and Wang H: Efficacy and safety of first-line immunotherapy plus chemotherapy in treating patients with extensive-stage small cell lung cancer: A Bayesian network meta-analysis. Front Immunol. 14:11970442023. View Article : Google Scholar : PubMed/NCBI

46 

da Cunha Santos G, Shepherd FA and Tsao MS: EGFR mutations and lung cancer. Annu Rev Pathol. 6:49–69. 2011. View Article : Google Scholar : PubMed/NCBI

47 

Paez JG, Jänne PA, Lee JC, Tracy S, Greulich H, Gabriel S, Herman P, Kaye FJ, Lindeman N, Boggon TJ, et al: EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 304:1497–1500. 2004. View Article : Google Scholar : PubMed/NCBI

48 

Liu X, Wang P, Zhang C and Ma Z: Epidermal growth factor receptor (EGFR): A rising star in the era of precision medicine of lung cancer. Oncotarget. 8:50209–50220. 2017. View Article : Google Scholar : PubMed/NCBI

49 

Agraso S, Lázaro M, Firvida XL, Santomé L, Fernández N, Azpitarte C, Leon L, Garcia C, Hudobro G, Areses MC, et al: Real-world data with afatinib in Spanish patients with treatment-naïve non-small-cell lung cancer harboring exon 19 deletions in epidermal growth factor receptor (Del19 EGFR): Clinical experience of the Galician lung cancer group. Cancer Treat Res Commun. 33:1006462022.PubMed/NCBI

50 

Matsui T, Tanizawa Y and Enatsu S: Exon 19 deletion and exon 21 L858R point mutation in EGFR Mutation-positive non-small cell lung cancer. Gan To Kagaku Ryoho. 48:673–676. 2021.(In Japanese). PubMed/NCBI

51 

Yu J, Zhang L, Peng J, Ward R, Hao P, Wang J, Zhang N, Yang Y, Guo X, Xiang C, et al: Dictamnine, a novel c-Met inhibitor, suppresses the proliferation of lung cancer cells by downregulating the PI3K/AKT/mTOR and MAPK signaling pathways. Biochem Pharmacol. 195:1148642022. View Article : Google Scholar : PubMed/NCBI

52 

Wen Z, Jiang R, Huang Y, Wen Z, Rui D, Liao X and Ling Z: Inhibition of lung cancer cells and Ras/Raf/MEK/ERK signal transduction by ectonucleoside triphosphate phosphohydrolase-7 (ENTPD7). Respir Res. 20:1942019. View Article : Google Scholar : PubMed/NCBI

53 

Qin BM, Chen X, Zhu JD and Pei DQ: Identification of EGFR kinase domain mutations among lung cancer patients in China: Implication for targeted cancer therapy. Cell Res. 15:212–217. 2005. View Article : Google Scholar : PubMed/NCBI

54 

Zhang Q, Dai HH, Dong HY, Sun CT, Yang Z and Han JQ: EGFR mutations and clinical outcomes of chemotherapy for advanced non-small cell lung cancer: A meta-analysis. Lung Cancer. 85:339–345. 2014. View Article : Google Scholar : PubMed/NCBI

55 

Wang C, Zhao K, Hu S, Dong W, Gong Y and Xie C: Clinical outcomes of afatinib versus osimertinib in patients with non-small cell lung cancer with uncommon EGFR mutations: A pooled analysis. Oncologist. 28:e397–e405. 2023. View Article : Google Scholar : PubMed/NCBI

56 

Sun H and Wu YL: Dacomitinib in non-small-cell lung cancer: A comprehensive review for clinical application. Future Oncol. 15:2769–2777. 2019. View Article : Google Scholar : PubMed/NCBI

57 

Leonetti A, Sharma S, Minari R, Perego P, Giovannetti E and Tiseo M: Resistance mechanisms to osimertinib in EGFR-mutated non-small cell lung cancer. Br J Cancer. 121:725–737. 2019. View Article : Google Scholar : PubMed/NCBI

58 

Skoulidis F and Papadimitrakopoulou VA: Targeting the gatekeeper: Osimertinib in EGFR T790M mutation-positive non-small cell lung cancer. Clin Cancer Res. 23:618–622. 2017. View Article : Google Scholar : PubMed/NCBI

59 

Spagnolo CC, Ciappina G, Giovannetti E, Squeri A, Granata B, Lazzari C, Pretelli G, Pasello G and Santarpia M: Targeting MET in non-small cell lung cancer (NSCLC): A new old story? Int J Mol Sci. 24:101192023. View Article : Google Scholar : PubMed/NCBI

60 

Oh DY and Bang YJ: HER2-targeted therapies-a role beyond breast cancer. Nat Rev Clin Oncol. 17:33–48. 2020. View Article : Google Scholar : PubMed/NCBI

61 

Yin X, Li Y, Wang H, Jia T, Wang E, Luo Y, Wei Y, Qin Z and Ma X: Small cell lung cancer transformation: From pathogenesis to treatment. Semin Cancer Biol. 86:595–606. 2022. View Article : Google Scholar : PubMed/NCBI

62 

Cheng WL, Feng PH, Lee KY, Chen KY, Sun WL, Van Hiep N, Luo CS and Wu SM: The role of EREG/EGFR pathway in tumor progression. Int J Mol Sci. 22:128282021. View Article : Google Scholar : PubMed/NCBI

63 

Iqbal MA, Arora S, Prakasam G, Calin GA and Syed MA: MicroRNA in lung cancer: Role, mechanisms, pathways and therapeutic relevance. Mol Aspects Med. 70:3–20. 2019. View Article : Google Scholar : PubMed/NCBI

64 

Lin L, Lu Q, Cao R, Ou Q, Ma Y, Bao H, Wu X, Shao Y, Wang Z and Shen B: Acquired rare recurrent EGFR mutations as mechanisms of resistance to osimertinib in lung cancer and in silico structural modelling. Am J Cancer Res. 10:4005–4015. 2020.PubMed/NCBI

65 

Mansour MA, AboulMagd AM, Abbas SH, Abdel-Rahman HM and Abdel-Aziz M: Insights into fourth generation selective inhibitors of (C797S) EGFR mutation combating non-small cell lung cancer resistance: A critical review. RSC Adv. 13:18825–18853. 2023. View Article : Google Scholar : PubMed/NCBI

66 

Singh D: Revolutionizing lung cancer treatment: Innovative CRISPR-Cas9 delivery strategies. AAPS PharmSciTech. 25:1292024. View Article : Google Scholar : PubMed/NCBI

67 

Li L, Jiang H, Zeng B, Wang X, Bao Y, Chen C, Ma L and Yuan J: Liquid biopsy in lung cancer. Clin Chim Acta. 554:1177572024. View Article : Google Scholar : PubMed/NCBI

68 

Hsu PC, Jablons DM, Yang CT and You L: Epidermal growth factor receptor (EGFR) pathway, yes-associated protein (YAP) and the regulation of programmed death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). Int J Mol Sci. 20:38212019. View Article : Google Scholar : PubMed/NCBI

69 

Elshatlawy M, Sampson J, Clarke K and Bayliss R: EML4-ALK biology and drug resistance in non-small cell lung cancer: A new phase of discoveries. Mol Oncol. 17:950–963. 2023. View Article : Google Scholar : PubMed/NCBI

70 

Camidge DR, Dziadziuszko R, Peters S, Mok T, Noe J, Nowicka M, Gadgeel SM, Cheema P, Pavlakis N, de Marinis F, et al: Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 14:1233–1243. 2019. View Article : Google Scholar : PubMed/NCBI

71 

Paliouras AR, Buzzetti M, Shi L, Donaldson IJ, Magee P, Sahoo S, Leong HS, Fassan M, Carter M, Di Leva G, et al: Vulnerability of drug-resistant EML4-ALK rearranged lung cancer to transcriptional inhibition. EMBO Mol Med. 12:e110992020. View Article : Google Scholar : PubMed/NCBI

72 

Li K, Liu Y, Ding Y, Zhang Z, Feng J, Hu J, Chen J, Lian Z, Chen Y, Hu K, et al: BCL6 is regulated by the MAPK/ELK1 axis and promotes KRAS-driven lung cancer. J Clin Invest. 132:e1613082022. View Article : Google Scholar : PubMed/NCBI

73 

Gadgeel SM and Wozniak A: Preclinical rationale for PI3K/Akt/mTOR pathway inhibitors as therapy for epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer. Clin Lung Cancer. 14:322–332. 2013. View Article : Google Scholar : PubMed/NCBI

74 

Shi L, Zhu W, Huang Y, Zhuo L, Wang S, Chen S, Zhang B and Ke B: Cancer-associated fibroblast-derived exosomal microRNA-20a suppresses the PTEN/PI3K-AKT pathway to promote the progression and chemoresistance of non-small cell lung cancer. Clin Transl Med. 12:e9892022. View Article : Google Scholar : PubMed/NCBI

75 

Tan AC and Tan DSW: Targeted therapies for lung cancer patients with oncogenic driver molecular alterations. J Clin Oncol. 40:611–625. 2022. View Article : Google Scholar : PubMed/NCBI

76 

Ahn MJ, Kim HR, Yang JCH, Han JY, Li JYC, Hochmair MJ, Chang GC, Delmonte A, Lee KH, Campelo RG, et al: Efficacy and safety of brigatinib compared with crizotinib in asian vs non-asian patients with locally advanced or metastatic ALK-inhibitor-naive ALK+ non-small cell lung cancer: Final results from the phase III ALTA-1L study. Clin Lung Cancer. 23:720–730. 2022. View Article : Google Scholar : PubMed/NCBI

77 

Mok T, Camidge DR, Gadgeel SM, Rosell R, Dziadziuszko R, Kim DW, Pérol M, Ou SHI, Ahn JS, Shaw AT, et al: Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 31:1056–1064. 2020. View Article : Google Scholar : PubMed/NCBI

78 

Baba K and Goto Y: Lorlatinib as a treatment for ALK-positive lung cancer. Future Oncol. 18:2745–2766. 2022. View Article : Google Scholar : PubMed/NCBI

79 

Lin JJ, Zhu VW, Yoda S, Yeap BY, Schrock AB, Dagogo-Jack I, Jessop NA, Jiang GY, Le LP, Gowen K, et al: Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 36:1199–1206. 2018. View Article : Google Scholar : PubMed/NCBI

80 

Pinto JA, Raez LE and Domingo G: Clinical consequences of resistance to ALK inhibitors in non-small cell lung cancer. Expert Rev Respir Med. 14:385–390. 2020. View Article : Google Scholar : PubMed/NCBI

81 

Shaw AT, Solomon BJ, Besse B, Bauer TM, Lin CC, Soo RA, Riely GJ, Ou SHI, Clancy JS, Li S, et al: ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 37:1370–1379. 2019. View Article : Google Scholar : PubMed/NCBI

82 

Desai A and Lovly CM: Strategies to overcome resistance to ALK inhibitors in non-small cell lung cancer: A narrative review. Transl Lung Cancer Res. 12:615–628. 2023. View Article : Google Scholar : PubMed/NCBI

83 

Balasundaram A and Doss GPC: A computational examination of the therapeutic advantages of fourth-generation ALK inhibitors TPX-0131 and repotrectinib over third-generation lorlatinib for NSCLC with ALK F1174C/L/V mutations. Front Mol Biosci. 10:13060462024. View Article : Google Scholar : PubMed/NCBI

84 

Golding B, Luu A, Jones R and Viloria-Petit AM: The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Mol Cancer. 17:522018. View Article : Google Scholar : PubMed/NCBI

85 

Torres-Jiménez J, Espinar JB, de Cabo HB, Berjaga MZ, Esteban-Villarrubia J, Fraile JZ and Paz-Ares L: Targeting KRAS(G12C) in non-small-cell lung cancer: Current standards and developments. Drugs. 84:527–548. 2024. View Article : Google Scholar : PubMed/NCBI

86 

Chang YS, Tu SJ, Chen YC, Liu TY, Lee YT, Yen JC, Fang HY and Chang JG: Mutation profile of non-small cell lung cancer revealed by next generation sequencing. Respir Res. 22:32021. View Article : Google Scholar : PubMed/NCBI

87 

Mugarza E, van Maldegem F, Boumelha J, Moore C, Rana S, Llorian Sopena M, East P, Ambler R, Anastasiou P, Romero-Clavijo P, et al: Therapeutic KRASG12C inhibition drives effective interferon-mediated antitumor immunity in immunogenic lung cancers. Sci Adv. 8:eabm87802022. View Article : Google Scholar : PubMed/NCBI

88 

Ceddia S, Landi L and Cappuzzo F: KRAS-mutant non-small-cell lung cancer: From past efforts to future challenges. Int J Mol Sci. 23:93912022. View Article : Google Scholar : PubMed/NCBI

89 

Bironzo P, Cani M, Jacobs F, Napoli VM, Listì A, Passiglia F, Righi L, Di Maio M, Novello S and Scagliotti GV: Real-world retrospective study of KRAS mutations in advanced non-small cell lung cancer in the era of immunotherapy. Cancer. 129:1662–1671. 2023. View Article : Google Scholar : PubMed/NCBI

90 

Ferrer I, Zugazagoitia J, Herbertz S, John W, Paz-Ares L and Schmid-Bindert G: KRAS-mutant non-small cell lung cancer: From biology to therapy. Lung Cancer. 124:53–64. 2018. View Article : Google Scholar : PubMed/NCBI

91 

Xu K, Park D, Magis AT, Zhang J, Zhou W, Sica GL, Ramalingam SS, Curran WJ and Deng X: Small molecule KRAS agonist for mutant KRAS cancer therapy. Mol Cancer. 18:852019. View Article : Google Scholar : PubMed/NCBI

92 

Brazel D, Arter Z and Nagasaka M: A long overdue targeted treatment for KRAS mutations in NSCLC: Spotlight on adagrasib. Lung Cancer (Auckl). 13:75–80. 2022.PubMed/NCBI

93 

Di Federico A, Ricciotti I, Favorito V, Michelina SV, Scaparone P, Metro G, De Giglio A, Pecci F, Lamberti G, Ambrogio C and Ricciuti B: Resistance to KRAS G12C inhibition in non-small cell lung cancer. Curr Oncol Rep. 25:1017–1029. 2023. View Article : Google Scholar : PubMed/NCBI

94 

Canon J, Rex K, Saiki AY, Mohr C, Cooke K, Bagal D, Gaida K, Holt T, Knutson CG, Koppada N, et al: The clinical KRAS(G12C) inhibitor AMG 510 drives anti-tumour immunity. Nature. 575:217–223. 2019. View Article : Google Scholar : PubMed/NCBI

95 

Lee A: Sotorasib: A review in KRAS G12C mutation-positive non-small cell lung cancer. Target Oncol. 17:727–733. 2022. View Article : Google Scholar : PubMed/NCBI

96 

Mausey N and Halford Z: Targeted therapies for previously ‘undruggable’ KRAS-mutated non-small cell lung cancer: A review of sotorasib and adagrasib. Ann Pharmacother. 58:622–635. 2024. View Article : Google Scholar : PubMed/NCBI

97 

Briere DM, Li S, Calinisan A, Sudhakar N, Aranda R, Hargis L, Peng DH, Deng J, Engstrom LD, Hallin J, et al: The KRASG12C inhibitor MRTX849 reconditions the tumor immune microenvironment and sensitizes tumors to checkpoint inhibitor therapy. Mol Cancer Ther. 20:975–985. 2021. View Article : Google Scholar : PubMed/NCBI

98 

Shi Z, Weng J, Niu H, Yang H, Liu R, Weng Y, Zhu Q, Zhang Y, Tao L, Wang Z, et al: D-1553: A novel KRASG12C inhibitor with potent and selective cellular and in vivo antitumor activity. Cancer Sci. 114:2951–2960. 2023. View Article : Google Scholar : PubMed/NCBI

99 

Santarpia M, Ciappina G, Spagnolo CC, Squeri A, Passalacqua MI, Aguilar A, Gonzalez-Cao M, Giovannetti E, Silvestris N and Rosell R: Targeted therapies for KRAS-mutant non-small cell lung cancer: From preclinical studies to clinical development-a narrative review. Transl Lung Cancer Res. 12:346–368. 2023. View Article : Google Scholar : PubMed/NCBI

100 

Yun J, Nakagawa R and Tham K: KRAS-targeted therapy in the treatment of non-small cell lung cancer. J Oncol Pharm Pract. 29:422–430. 2023. View Article : Google Scholar : PubMed/NCBI

101 

Corral de la Fuente E, Olmedo Garcia ME, Gomez Rueda A, Lage Y and Garrido P: Targeting KRAS in non-small cell lung cancer. Front Oncol. 11:7926352022. View Article : Google Scholar : PubMed/NCBI

102 

Tomasini P, Walia P, Labbe C, Jao K and Leighl NB: Targeting the KRAS pathway in non-small cell lung cancer. Oncologist. 21:1450–1460. 2016. View Article : Google Scholar : PubMed/NCBI

103 

Li XQ, Cheng XJ, Wu J, Wu KF and Liu T: Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer. Cell Mol Biol Lett. 29:582024. View Article : Google Scholar : PubMed/NCBI

104 

Gong G, Ganesan K, Xiong Q and Zheng Y: Antitumor effects of ononin by modulation of apoptosis in non-small-cell lung cancer through inhibiting PI3K/Akt/mTOR pathway. Oxid Med Cell Longev. 2022:51224482022. View Article : Google Scholar : PubMed/NCBI

105 

Chandarlapaty S, Sawai A, Scaltriti M, Rodrik-Outmezguine V, Grbovic-Huezo O, Serra V, Majumder PK, Baselga J and Rosen N: AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell. 19:58–71. 2011. View Article : Google Scholar : PubMed/NCBI

106 

Bellmunt J, Maroto P, Bonfill T, Vazquez F, Perez-Gracia JL, Juanpere N, Hernandez-Prat A, Hernandez-Llodra S, Rovira A, Juan O and Rodriguez-Vida A: Dual mTOR1/2 inhibitor sapanisertib (FTH-003/TAK-228) in combination with weekly paclitaxel in patients with previously treated metastatic urothelial carcinoma: A phase II open-label study: A phase II open-label study. Clin Genitourin Cancer. 22:1021232024. View Article : Google Scholar : PubMed/NCBI

107 

Al-Bustany HA, Muhammad HA, Chawsheen MA and Dash PR: Fenretinide induces apoptosis and synergises the apoptosis inducing effect of gemcitabine through inhibition of key signalling molecules involved in A549 cell survival in in silico and in vitro analyses. Cell Signal. 111:1108852023. View Article : Google Scholar : PubMed/NCBI

108 

Curless BP, Uko NE and Matesic DF: Modulator of the PI3K/Akt oncogenic pathway affects mTOR complex 2 in human adenocarcinoma cells. Invest New Drugs. 37:902–911. 2019. View Article : Google Scholar : PubMed/NCBI

109 

Fang W, Huang Y, Gu W, Gan J, Wang W, Zhang S, Wang K, Zhan J, Yang Y, Huang Y, et al: PI3K-AKT-mTOR pathway alterations in advanced NSCLC patients after progression on EGFR-TKI and clinical response to EGFR-TKI plus everolimus combination therapy. Transl Lung Cancer Res. 9:1258–1267. 2020. View Article : Google Scholar : PubMed/NCBI

110 

Pal I and Mandal M: PI3K and Akt as molecular targets for cancer therapy: Current clinical outcomes. Acta Pharmacol Sin. 33:1441–1458. 2012. View Article : Google Scholar : PubMed/NCBI

111 

Xu Y, Hu Y, Xu T, Yan K, Zhang T, Li Q, Chang F, Guo X, Peng J, Li M, et al: RNF8-mediated regulation of Akt promotes lung cancer cell survival and resistance to DNA damage. Cell Rep. 37:1098542021. View Article : Google Scholar : PubMed/NCBI

112 

He YM, Zhou XM, Jiang SY, Zhang ZB, Cao BY, Liu JB, Zeng YY, Zhao J and Mao XL: TRIM25 activates AKT/mTOR by inhibiting PTEN via K63-linked polyubiquitination in non-small cell lung cancer. Acta Pharmacol Sin. 43:681–691. 2022. View Article : Google Scholar : PubMed/NCBI

113 

Alharbi KS, Shaikh MAJ, Almalki WH, Kazmi I, Al-Abbasi FA, Alzarea SI, Imam SS, Alshehri S, Ghoneim MM, Singh SK, et al: PI3K/Akt/mTOR pathways inhibitors with potential prospects in non-small-cell lung cancer. J Environ Pathol Toxicol Oncol. 41:85–102. 2022. View Article : Google Scholar : PubMed/NCBI

114 

Yan D, Huelse JM, Kireev D, Tan Z, Chen L, Goyal S, Wang X, Frye SV, Behera M, Schneider F, et al: MERTK activation drives osimertinib resistance in EGFR-mutant non-small cell lung cancer. J Clin Invest. 132:e1505172022. View Article : Google Scholar : PubMed/NCBI

115 

Coco S, Truini A, Alama A, Dal Bello MG, Venè R, Garuti A, Carminati E, Rijavec E, Genova C, Barletta G, et al: Afatinib resistance in non-small cell lung cancer involves the PI3K/AKT and MAPK/ERK signalling pathways and epithelial-to-mesenchymal transition. Target Oncol. 10:393–404. 2015. View Article : Google Scholar : PubMed/NCBI

116 

Adachi Y, Watanabe K, Kita K, Kitai H, Kotani H, Sato Y, Inase N, Yano S and Ebi H: Resistance mediated by alternative receptor tyrosine kinases in FGFR1-amplified lung cancer. Carcinogenesis. 38:1063–1072. 2017. View Article : Google Scholar : PubMed/NCBI

117 

Yu Y, Shang Y, Shi S, He Y, Shi W, Wang M, Wang Q, Xu D, Shi C and Chen H: Combination of arsenic trioxide and apatinib synergistically inhibits small cell lung cancer by down-regulating VEGFR2/mTOR and Akt/c-Myc signaling pathway via GRB10. Hereditas. 161:292024. View Article : Google Scholar : PubMed/NCBI

118 

Wu YY, Wu HC, Wu JE, Huang KY, Yang SC, Chen SX, Tsao CJ, Hsu KF, Chen YL and Hong TM: The dual PI3K/mTOR inhibitor BEZ235 restricts the growth of lung cancer tumors regardless of EGFR status, as a potent accompanist in combined therapeutic regimens. J Exp Clin Cancer Res. 38:2822019. View Article : Google Scholar : PubMed/NCBI

119 

Zhang J, Hong Y and Shen J: Combination treatment with perifosine and MEK-162 demonstrates synergism against lung cancer cells in vitro and in vivo. Tumour Biol. 36:5699–5706. 2015. View Article : Google Scholar : PubMed/NCBI

120 

Quan Z, Yang Y, Zheng H, Zhan Y, Luo J, Ning Y and Fan S: Clinical implications of the interaction between PD-1/PD-L1 and PI3K/AKT/mTOR pathway in progression and treatment of non-small cell lung cancer. J Cancer. 13:3434–3443. 2022. View Article : Google Scholar : PubMed/NCBI

121 

Wu J, Zhao X, Sun Q, Jiang Y, Zhang W, Luo J and Li Y: Synergic effect of PD-1 blockade and endostar on the PI3K/AKT/mTOR-mediated autophagy and angiogenesis in Lewis lung carcinoma mouse model. Biomed Pharmacother. 125:1097462020. View Article : Google Scholar : PubMed/NCBI

122 

Liu Q, Chen X, Qi M, Li Y, Chen W and Zhang C, Wang J, Han Z and Zhang C: Combined cryoablation and PD-1 inhibitor synergistically enhance antitumor immune responses in Lewis lung adenocarcinoma mice via the PI3K/AKT/mTOR pathway. Biochim Biophys Acta Mol Basis Dis. 1870:1672622024. View Article : Google Scholar : PubMed/NCBI

123 

Shi Z, Shen Y, Liu X and Zhang S: Sinensetin inhibits the movement ability and tumor immune microenvironment of non-small cell lung cancer through the inactivation of AKT/β-catenin axis. J Biochem Mol Toxicol. 38:e700242024. View Article : Google Scholar : PubMed/NCBI

124 

Santini FC and Hellmann MD: PD-1/PD-L1 axis in lung cancer. Cancer J. 24:15–19. 2018. View Article : Google Scholar : PubMed/NCBI

125 

Kumar R, Collins D, Dolly S, McDonald F, O'Brien MER and Yap TA: Targeting the PD-1/PD-L1 axis in non-small cell lung cancer. Curr Probl Cancer. 41:111–124. 2017. View Article : Google Scholar : PubMed/NCBI

126 

Yadav R, Khatkar R, Yap KCH, Kang CYH, Lyu J, Singh RK, Mandal S, Mohanta A, Lam HY, Okina E, et al: The miRNA and PD-1/PD-L1 signaling axis: An arsenal of immunotherapeutic targets against lung cancer. Cell Death Discov. 10:4142024. View Article : Google Scholar : PubMed/NCBI

127 

Lu M, Wang K, Ji W, Yu Y, Li Z, Xia W and Lu S: FGFR1 promotes tumor immune evasion via YAP-mediated PD-L1 expression upregulation in lung squamous cell carcinoma. Cell Immunol. 379:1045772022. View Article : Google Scholar : PubMed/NCBI

128 

Qiao M, Jiang T, Liu X, Mao S, Zhou F, Li X, Zhao C, Chen X, Su C, Ren S and Zhou C: Immune checkpoint inhibitors in EGFR-mutated NSCLC: Dusk or dawn? J Thorac Oncol. 16:1267–1288. 2021. View Article : Google Scholar : PubMed/NCBI

129 

Genova C, Dellepiane C, Carrega P, Sommariva S, Ferlazzo G, Pronzato P, Gangemi R, Filaci G, Coco S and Croce M: Therapeutic implications of tumor microenvironment in lung cancer: Focus on immune checkpoint blockade. Front Immunol. 12:7994552022. View Article : Google Scholar : PubMed/NCBI

130 

Sholl LM: Biomarkers of response to checkpoint inhibitors beyond PD-L1 in lung cancer. Mod Pathol. 35 (Suppl 1):S66–S74. 2022. View Article : Google Scholar

131 

Reck M, Rodríguez-Abreu D, Robinson AG, Hui R, Csőszi T, Fülöp A, Gottfried M, Peled N, Tafreshi A, Cuffe S, et al: Updated analysis of KEYNOTE-024: Pembrolizumab versus platinum-based chemotherapy for advanced non-small-cell lung cancer with PD-L1 tumor proportion score of 50% or greater. J Clin Oncol. 37:537–546. 2019. View Article : Google Scholar : PubMed/NCBI

132 

Ready NE, Ott PA, Hellmann MD, Zugazagoitia J, Hann CL, de Braud F, Antonia SJ, Ascierto PA, Moreno V, Atmaca A, et al: Nivolumab monotherapy and nivolumab plus ipilimumab in recurrent small cell lung cancer: Results from the checkmate 032 randomized cohort. J Thorac Oncol. 15:426–435. 2020. View Article : Google Scholar : PubMed/NCBI

133 

Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, et al: Updated overall survival and PD-L1 subgroup analysis of patients with extensive-stage small-cell lung cancer treated with atezolizumab, carboplatin, and etoposide (IMpower133). J Clin Oncol. 39:619–630. 2021. View Article : Google Scholar : PubMed/NCBI

134 

Tang S, Qin C, Hu H, Liu T, He Y, Guo H, Yan H, Zhang J, Tang S and Zhou H: Immune checkpoint inhibitors in non-small cell lung cancer: Progress, challenges, and prospects. Cells. 11:3202022. View Article : Google Scholar : PubMed/NCBI

135 

Passaro A, Brahmer J, Antonia S, Mok T and Peters S: Managing resistance to immune checkpoint inhibitors in lung cancer: Treatment and novel strategies. J Clin Oncol. 40:598–610. 2022. View Article : Google Scholar : PubMed/NCBI

136 

Kejamurthy P and Devi KTR: Immune checkpoint inhibitors and cancer immunotherapy by aptamers: An overview. Med Oncol. 41:402023. View Article : Google Scholar : PubMed/NCBI

137 

Li Y, Jiang M, Aye L, Luo L, Zhang Y, Xu F, Wei Y, Peng D, He X, Gu J, et al: UPP1 promotes lung adenocarcinoma progression through the induction of an immunosuppressive microenvironment. Nat Commun. 15:12002024. View Article : Google Scholar : PubMed/NCBI

138 

Ghorani E, Swanton C and Quezada SA: Cancer cell-intrinsic mechanisms driving acquired immune tolerance. Immunity. 56:2270–2295. 2023. View Article : Google Scholar : PubMed/NCBI

139 

Giatromanolaki A, Kouroupi M, Pouliliou S, Mitrakas A, Hasan F, Pappa A and Koukourakis MI: Ectonucleotidase CD73 and CD39 expression in non-small cell lung cancer relates to hypoxia and immunosuppressive pathways. Life Sci. 259:1183892020. View Article : Google Scholar : PubMed/NCBI

140 

Best SA, Gubser PM, Sethumadhavan S, Kersbergen A, Negrón Abril YL, Goldford J, Sellers K, Abeysekera W, Garnham AL, McDonald JA, et al: Glutaminase inhibition impairs CD8 T cell activation in STK11-/Lkb1-deficient lung cancer. Cell Metab. 34:874–887.e6. 2022. View Article : Google Scholar : PubMed/NCBI

141 

Zhu M, Kim J, Deng Q, Ricciuti B, Alessi JV, Eglenen-Polat B, Bender ME, Huang HC, Kowash RR, Cuevas I, et al: Loss of p53 and mutational heterogeneity drives immune resistance in an autochthonous mouse lung cancer model with high tumor mutational burden. Cancer Cell. 41:1731–1748.e8. 2023. View Article : Google Scholar : PubMed/NCBI

142 

Zhu C, Zhuang W, Chen L, Yang W and Ou WB: Frontiers of ctDNA, targeted therapies, and immunotherapy in non-small-cell lung cancer. Transl Lung Cancer Res. 9:111–138. 2020. View Article : Google Scholar : PubMed/NCBI

143 

Chu X, Tian W, Wang Z, Zhang J and Zhou R: Co-inhibition of TIGIT and PD-1/PD-L1 in cancer immunotherapy: Mechanisms and clinical trials. Mol Cancer. 22:932023. View Article : Google Scholar : PubMed/NCBI

144 

Chen Y, Chen Z, Chen R, Fang C, Zhang C, Ji M and Yang X: Immunotherapy-based combination strategies for treatment of EGFR-TKI-resistant non-small-cell lung cancer. Future Oncol. 18:1757–1775. 2022. View Article : Google Scholar : PubMed/NCBI

145 

West HJ, McCleland M, Cappuzzo F, Reck M, Mok TS, Jotte RM, Nishio M, Kim E, Morris S, Zou W, et al: Clinical efficacy of atezolizumab plus bevacizumab and chemotherapy in KRAS-mutated non-small cell lung cancer with STK11, KEAP1, or TP53 comutations: Subgroup results from the phase III IMpower150 trial. J Immunother Cancer. 10:e0030272022. View Article : Google Scholar : PubMed/NCBI

146 

Judd J and Borghaei H: Combining immunotherapy and chemotherapy for non-small cell lung cancer. Thorac Surg Clin. 30:199–206. 2020. View Article : Google Scholar : PubMed/NCBI

147 

Shang S, Liu J, Verma V, Wu M, Welsh J, Yu J and Chen D: Combined treatment of non-small cell lung cancer using radiotherapy and immunotherapy: Challenges and updates. Cancer Commun (Lond). 41:1086–1099. 2021. View Article : Google Scholar : PubMed/NCBI

148 

Chae YK, Arya A, Iams W, Cruz M, Mohindra N, Villaflor V and Giles FJ: Immune checkpoint pathways in non-small cell lung cancer. Ann Transl Med. 6:882018. View Article : Google Scholar : PubMed/NCBI

149 

Raghav KPS and Moasser MM: Molecular pathways and mechanisms of HER2 in cancer therapy. Clin Cancer Res. 29:2351–2361. 2023. View Article : Google Scholar : PubMed/NCBI

150 

Nützinger J, Bum Lee J, Li Low J, Ling Chia P, Talisa Wijaya S, Chul Cho B, Min Lim S and Soo RA: Management of HER2 alterations in non-small cell lung cancer-the past, present, and future. Lung Cancer. 186:1073852023. View Article : Google Scholar : PubMed/NCBI

151 

Riudavets M, Sullivan I, Abdayem P and Planchard D: Targeting HER2 in non-small-cell lung cancer (NSCLC): A glimpse of hope? An updated review on therapeutic strategies in NSCLC harbouring HER2 alterations. ESMO Open. 6:1002602021. View Article : Google Scholar : PubMed/NCBI

152 

Ghezzi C, Chen BY, Damoiseaux R and Clark PM: Pacritinib inhibits glucose consumption in squamous cell lung cancer cells by targeting. FLT3.Sci Rep. 13:14422023. View Article : Google Scholar : PubMed/NCBI

153 

Kuncman Ł, Orzechowska M, Milecki T, Kucharz J and Fijuth J: High FLT3 expression increases immune-cell infiltration in the tumor microenvironment and correlates with prolonged disease-free survival in patients with non-small cell lung cancer. Mol Oncol. 18:1316–1326. 2024. View Article : Google Scholar : PubMed/NCBI

154 

Dhillon S: Gilteritinib: First global approval. Drugs. 79:331–339. 2019. View Article : Google Scholar : PubMed/NCBI

155 

Hu C, Zhang Y, Yang J, Xu Y, Deng T, Li Y, Xu S, Wang S and Wang P: Ningetinib, a novel FLT3 inhibitor, overcomes secondary drug resistance in acute myeloid leukemia. Cell Commun Signal. 22:3552024. View Article : Google Scholar : PubMed/NCBI

156 

Bruner JK, Ma HS, Li L, Qin ACR, Rudek MA, Jones RJ, Levis MJ, Pratz KW, Pratilas CA and Small D: Adaptation to TKI treatment reactivates ERK signaling in tyrosine kinase-driven leukemias and other malignancies. Cancer Res. 77:5554–5563. 2017. View Article : Google Scholar : PubMed/NCBI

157 

He L, Wang X, Liu K, Wu X, Yang X, Song G, Zhang B and Zhong L: Integrative PDGF/PDGFR and focal adhesion pathways are downregulated in ERCC1-defective non-small cell lung cancer undergoing sodium glycididazole-sensitized cisplatin treatment. Gene. 691:70–76. 2019. View Article : Google Scholar : PubMed/NCBI

158 

Catena R, Luis-Ravelo D, Antón I, Zandueta C, Salazar-Colocho P, Larzábal L, Calvo A and Lecanda F: PDGFR signaling blockade in marrow stroma impairs lung cancer bone metastasis. Cancer Res. 71:164–174. 2011. View Article : Google Scholar : PubMed/NCBI

159 

Riess JW and Neal JW: Targeting FGFR, ephrins, Mer, MET, and PDGFR-α in non-small cell lung cancer. J Thorac Oncol. 6 (11 Suppl 4):S1797–S1798. 2011. View Article : Google Scholar : PubMed/NCBI

160 

Kranthi Reddy S, Reddy SVG and Hussain Basha S: Discovery of novel PDGFR inhibitors targeting non-small cell lung cancer using a multistep machine learning assisted hybrid virtual screening approach. RSC Adv. 15:851–869. 2025. View Article : Google Scholar : PubMed/NCBI

161 

Xuan H, Jingshu G, Fang Y, Na L, Xiaolin S, Zhaoyang Y, Meng W and Gongyan C: Somatic mutation of KIT is rare in small cell lung cancer patients from Northeast China. Histol Histopathol. 29:273–278. 2014.PubMed/NCBI

162 

Miettinen M and Lasota J: KIT (CD117): A review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 13:205–220. 2005. View Article : Google Scholar : PubMed/NCBI

163 

Funkhouser AT, Strigenz AM, Blair BB, Miller AP, Shealy JC, Ewing JA, Martin JC, Funk CR, Edenfield WJ and Blenda AV: KIT mutations correlate with higher galectin levels and brain metastasis in breast and non-small cell lung cancer. Cancers (Basel). 14:27812022. View Article : Google Scholar : PubMed/NCBI

164 

Yang L, Zhou F, Zheng D, Wang D, Li X, Zhao C and Huang X: FGF/FGFR signaling: From lung development to respiratory diseases. Cytokine Growth Factor Rev. 62:94–104. 2021. View Article : Google Scholar : PubMed/NCBI

165 

Pacini L, Jenks AD, Lima NC and Huang PH: Targeting the fibroblast growth factor receptor (FGFR) family in lung cancer. Cells. 10:11542021. View Article : Google Scholar : PubMed/NCBI

166 

Desai A and Adjei AA: FGFR signaling as a target for lung cancer therapy. J Thorac Oncol. 11:9–20. 2016. View Article : Google Scholar : PubMed/NCBI

167 

Peng M, Deng J and Li X: Clinical advances and challenges in targeting FGF/FGFR signaling in lung cancer. Mol Cancer. 23:2562024. View Article : Google Scholar : PubMed/NCBI

168 

Biello F, Burrafato G, Rijavec E, Genova C, Barletta G, Truini A, Coco S, Bello MG, Alama A, Boccardo F and Grossi F: Fibroblast growth factor receptor (FGFR): A new target for non-small cell lung cancer therapy. Anticancer Agents Med Chem. 16:1142–1154. 2016. View Article : Google Scholar : PubMed/NCBI

169 

Cervantes-Villagrana RD, Mendoza V, Hinck CS, de la Fuente-León RL, Hinck AP, Reyes-Cruz G, Vázquez-Prado J and López-Casillas F: Betaglycan sustains HGF/Met signaling in lung cancer and endothelial cells promoting cell migration and tumor growth. Heliyon. 10:e305202024. View Article : Google Scholar : PubMed/NCBI

170 

Huang G, Liu X, Jiang T, Cao Y, Sang M, Song X, Zhou B, Qu H, Cai H, Xing D, et al: Luteolin overcomes acquired resistance to osimertinib in non-small cell lung cancer cells by targeting the HGF-MET-Akt pathway. Am J Cancer Res. 13:4145–4162. 2023.PubMed/NCBI

171 

Moosavi F, Giovannetti E, Peters GJ and Firuzi O: Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer. Crit Rev Oncol Hematol. 160:1032342021. View Article : Google Scholar : PubMed/NCBI

172 

Yin J, Hu W, Fu W, Dai L, Jiang Z, Zhong S, Deng B and Zhao J: HGF/MET regulated epithelial-mesenchymal transitions and metastasis by FOSL2 in non-small cell lung cancer. Onco Targets Ther. 12:9227–9237. 2019. View Article : Google Scholar : PubMed/NCBI

173 

Fregni M, Ciribilli Y and Zawacka-Pankau JE: The therapeutic potential of the restoration of the p53 protein family members in the EGFR-mutated lung cancer. Int J Mol Sci. 23:72132022. View Article : Google Scholar : PubMed/NCBI

174 

Lin CC, Liao WT, Yang TY, Lu HJ, Hsu SL and Wu CC: MicroRNA-10b modulates cisplatin tolerance by targeting p53 directly in lung cancer cells. Oncol Rep. 46:1672021. View Article : Google Scholar : PubMed/NCBI

175 

Zhang H, Zhang G, Xiao M, Cui S, Jin C, Yang J, Wu S and Lu X: Two-polarized roles of transcription factor FOSB in lung cancer progression and prognosis: Dependent on p53 status. J Exp Clin Cancer Res. 43:2372024. View Article : Google Scholar : PubMed/NCBI

176 

Chantarawong W, Kuncharoen N, Tanasupawat S and Chanvorachote P: Lumichrome inhibits human lung cancer cell growth and induces apoptosis via a p53-dependent mechanism. Nutr Cancer. 71:1390–1402. 2019. View Article : Google Scholar : PubMed/NCBI

177 

Li L, Li P, Ma X, Zeng S, Peng Y and Zhang G: Therapeutic restoring p53 function with small molecule for oncogene-driven non-small cell lung cancer by targeting serine 392 phosphorylation. Biochem Pharmacol. 203:1151882022. View Article : Google Scholar : PubMed/NCBI

178 

Wang J, Liu D, Sun Z, Ye T, Li J, Zeng B, Zhao Q and Rosie Xing H: Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53. Cell Death Dis. 12:982021. View Article : Google Scholar : PubMed/NCBI

179 

Tang X, Li Y, Liu L, Guo R, Zhang P, Zhang Y, Zhang Y, Zhao J, Su J, Sun L and Liu Y: Sirtuin 3 induces apoptosis and necroptosis by regulating mutant p53 expression in small-cell lung cancer. Oncol Rep. 43:591–600. 2020.PubMed/NCBI

180 

Krishnamurthy N and Kurzrock R: Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 62:50–60. 2018. View Article : Google Scholar : PubMed/NCBI

181 

He Y, Jiang X, Duan L, Xiong Q, Yuan Y, Liu P, Jiang L, Shen Q, Zhao S, Yang C and Chen Y: LncRNA PKMYT1AR promotes cancer stem cell maintenance in non-small cell lung cancer via activating Wnt signaling pathway. Mol Cancer. 20:1562021. View Article : Google Scholar : PubMed/NCBI

182 

Li HJ, Ke FY, Lin CC, Lu MY, Kuo YH, Wang YP, Liang KH, Lin SC, Chang YH, Chen HY, et al: ENO1 promotes lung cancer metastasis via HGFR and WNT signaling-driven epithelial-to-mesenchymal transition. Cancer Res. 81:4094–4109. 2021. View Article : Google Scholar : PubMed/NCBI

183 

Li Z, Wu S and Liu W: Advances of Wnt/β-catenin signaling pathway in lung cancer: A review. Altern Ther Health Med. 30:238–247. 2024.

184 

Chen J, Wang D, Chen H, Gu J, Jiang X, Han F, Cao J, Liu W and Liu J: TMEM196 inhibits lung cancer metastasis by regulating the Wnt/β-catenin signaling pathway. J Cancer Res Clin Oncol. 149:653–667. 2023. View Article : Google Scholar : PubMed/NCBI

185 

Shen Y, Yang Y, Zhao Y, Nuerlan S, Zhan Y and Liu C: YY1/circCTNNB1/miR-186-5p/YY1 positive loop aggravates lung cancer progression through the Wnt pathway. Epigenetics. 19:23690062024. View Article : Google Scholar : PubMed/NCBI

186 

Malyla V, Paudel KR, De Rubis G, Hansbro NG, Hansbro PM and Dua K: Cigarette smoking induces lung cancer tumorigenesis via upregulation of the WNT/β-catenin signaling pathway. Life Sci. 326:1217872023. View Article : Google Scholar : PubMed/NCBI

187 

Yang J, Chen J, He J, Li J, Shi J, Cho WC and Liu X: Wnt signaling as potential therapeutic target in lung cancer. Expert Opin Ther Targets. 20:999–1015. 2016. View Article : Google Scholar : PubMed/NCBI

188 

Zhang Y and Wang X: Targeting the Wnt/β-catenin signaling pathway in cancer. J Hematol Oncol. 13:1652020. View Article : Google Scholar : PubMed/NCBI

189 

Bugter JM, Fenderico N and Maurice MM: Mutations and mechanisms of WNT pathway tumour suppressors in cancer. Nat Rev Cancer. 21:5–21. 2021. View Article : Google Scholar : PubMed/NCBI

190 

Neiheisel A, Kaur M, Ma N, Havard P and Shenoy AK: Wnt pathway modulators in cancer therapeutics: An update on completed and ongoing clinical trials. Int J Cancer. 150:727–740. 2022. View Article : Google Scholar : PubMed/NCBI

191 

Song P, Gao Z, Bao Y, Chen L, Huang Y, Liu Y, Dong Q and Wei X: Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J Hematol Oncol. 17:462024. View Article : Google Scholar : PubMed/NCBI

192 

Xue C, Yao Q, Gu X, Shi Q, Yuan X, Chu Q, Bao Z, Lu J and Li L: Evolving cognition of the JAK-STAT signaling pathway: Autoimmune disorders and cancer. Signal Transduct Target Ther. 8:2042023. View Article : Google Scholar : PubMed/NCBI

193 

Hu X, Li J, Fu M, Zhao X and Wang W: The JAK/STAT signaling pathway: From bench to clinic. Signal Transduct Target Ther. 6:4022021. View Article : Google Scholar : PubMed/NCBI

194 

Erdogan F, Radu TB, Orlova A, Qadree AK, de Araujo ED, Israelian J, Valent P, Mustjoki SM, Herling M, Moriggl R and Gunning PT: JAK-STAT core cancer pathway: An integrative cancer interactome analysis. J Cell Mol Med. 26:2049–2062. 2022. View Article : Google Scholar : PubMed/NCBI

195 

Shen M, Xu Z, Xu W, Jiang K, Zhang F, Ding Q, Xu Z and Chen Y: Inhibition of ATM reverses EMT and decreases metastatic potential of cisplatin-resistant lung cancer cells through JAK/STAT3/PD-L1 pathway. J Exp Clin Cancer Res. 38:1492019. View Article : Google Scholar : PubMed/NCBI

196 

Wu Q, Wu W, Fu B, Shi L, Wang X and Kuca K: JNK signaling in cancer cell survival. Med Res Rev. 39:2082–2104. 2019. View Article : Google Scholar : PubMed/NCBI

197 

Patel MR, Dash A, Jacobson BA, Ji Y, Baumann D, Ismail K and Kratzke RA: JAK/STAT inhibition with ruxolitinib enhances oncolytic virotherapy in non-small cell lung cancer models. Cancer Gene Ther. 26:411–418. 2019. View Article : Google Scholar : PubMed/NCBI

198 

Ding Y, Yuan X, Wang Y and Yan J: CASQ2 alleviates lung cancer by inhibiting M2 tumor-associated macrophage polarization and JAK/STAT pathway. J Biochem Mol Toxicol. 38:e238012024. View Article : Google Scholar : PubMed/NCBI

199 

Saito A, Horie M and Nagase T: TGF-β signaling in lung health and disease. Int J Mol Sci. 19:24602018. View Article : Google Scholar : PubMed/NCBI

200 

Kim BN, Ahn DH, Kang N, Yeo CD, Kim YK, Lee KY, Kim TJ, Lee SH, Park MS, Yim HW, et al: TGF-β induced EMT and stemness characteristics are associated with epigenetic regulation in lung cancer. Sci Rep. 10:105972020. View Article : Google Scholar : PubMed/NCBI

201 

Huang Y, Chen Z, Lu T, Bi G, Li M, Liang J, Hu Z, Zheng Y, Yin J, Xi J, et al: HIF-1α switches the functionality of TGF-β signaling via changing the partners of smads to drive glucose metabolic reprogramming in non-small cell lung cancer. J Exp Clin Cancer Res. 40:3982021. View Article : Google Scholar : PubMed/NCBI

202 

Deng X, Ma N, He J, Xu F and Zou G: The role of TGFBR3 in the development of lung cancer. Protein Pept Lett. 31:491–503. 2024. View Article : Google Scholar : PubMed/NCBI

203 

Li J, Shen C, Wang X, Lai Y, Zhou K, Li P, Liu L and Che G: Prognostic value of TGF-beta in lung cancer: Systematic review and meta-analysis. BMC Cancer. 19:6912019. View Article : Google Scholar : PubMed/NCBI

204 

Lai XN, Li J, Tang LB, Chen WT, Zhang L and Xiong LX: MiRNAs and LncRNAs: Dual roles in TGF-β signaling-regulated metastasis in lung cancer. Int J Mol Sci. 21:11932020. View Article : Google Scholar : PubMed/NCBI

205 

Cui Z, Ruan Z, Li M, Ren R, Ma Y, Zeng J, Sun J, Ye W, Xu W, Guo X, et al: Obstructive sleep apnea promotes the progression of lung cancer by modulating cancer cell invasion and cancer-associated fibroblast activation via TGFβ signaling. Redox Rep. 28:22798132023. View Article : Google Scholar : PubMed/NCBI

206 

Hedrick E, Mohankumar K and Safe S: TGFβ-induced lung cancer cell migration is NR4A1-dependent. Mol Cancer Res. 16:1991–2002. 2018. View Article : Google Scholar : PubMed/NCBI

207 

Saito A, Horie M, Micke P and Nagase T: The role of TGF-β signaling in lung cancer associated with idiopathic pulmonary fibrosis. Int J Mol Sci. 19:36112018. View Article : Google Scholar : PubMed/NCBI

208 

Yin Y, Dai H, Sun X, Xi Z, Zhang J, Pan Y, Huang Y, Ma X, Xia Q and He K: HRG inhibits liver cancer lung metastasis by suppressing neutrophil extracellular trap formation. Clin Transl Med. 13:e12832023. View Article : Google Scholar : PubMed/NCBI

209 

Liu W, Wang H, Bai F, Ding L, Huang Y, Lu C, Chen S, Li C, Yue X, Liang X, et al: IL-6 promotes metastasis of non-small-cell lung cancer by up-regulating TIM-4 via NF-κB. Cell Prolif. 53:e127762020. View Article : Google Scholar : PubMed/NCBI

210 

Wang Y, Liu F, Chen L, Fang C, Li S, Yuan S, Qian X, Yin Y, Yu B, Fu B, et al: Neutrophil extracellular traps (NETs) promote non-small cell lung cancer metastasis by suppressing lncRNA MIR503HG to activate the NF-κB/NLRP3 inflammasome pathway. Front Immunol. 13:8675162022. View Article : Google Scholar : PubMed/NCBI

211 

Zhang J, Zhao K, Zhou W, Kang R, Wei S, Shu Y, Yu C, Ku Y, Mao Y, Luo H, et al: Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer. Signal Transduct Target Ther. 9:652024. View Article : Google Scholar : PubMed/NCBI

212 

Rasmi RR, Sakthivel KM and Guruvayoorappan C: NF-κB inhibitors in treatment and prevention of lung cancer. Biomed Pharmacother. 130:1105692020. View Article : Google Scholar : PubMed/NCBI

213 

Liu X, Liu X, Zhuo C, Shen J, Lu K, Sha M, Ye J, Huang J, Han H and Yu H: NAT10 promotes malignant progression of lung cancer via the NF-κB signaling pathway. Discov Med. 35:936–945. 2023. View Article : Google Scholar : PubMed/NCBI

214 

Wei X, Liu Z, Shen Y, Dong H, Chen K, Shi X, Chen Y, Wang B and Dong S: Semaphorin4A promotes lung cancer by activation of NF-κB pathway mediated by PlexinB1. PeerJ. 11:e162922023. View Article : Google Scholar : PubMed/NCBI

215 

Dimitrakopoulos FD, Kottorou AE, Kalofonou M and Kalofonos HP: The fire within: NF-κB involvement in non-small cell lung cancer. Cancer Res. 80:4025–4036. 2020. View Article : Google Scholar : PubMed/NCBI

216 

Li Y, Zu L, Wu H, Zhang F, Fan Y, Pan H, Du X, Guo F and Zhou Q: MiR-192/NKRF axis confers lung cancer cell chemoresistance to cisplatin via the NF-κB pathway. Thorac Cancer. 13:430–441. 2022. View Article : Google Scholar : PubMed/NCBI

217 

Jin Y, Zhang Y, Huang A, Chen Y, Wang J, Liu N, Wang X, Gong Y, Wang W and Pan J: Overexpression of SERPINA3 suppresses tumor progression by modulating SPOP/NF-κB in lung cancer. Int J Oncol. 63:962023. View Article : Google Scholar : PubMed/NCBI

218 

Wang Y, Zhang J, Li YJ, Yu NN, Liu WT, Liang JZ, Xu WW, Sun ZH, Li B and He QY: MEST promotes lung cancer invasion and metastasis by interacting with VCP to activate NF-κB signaling. J Exp Clin Cancer Res. 40:3012021. View Article : Google Scholar : PubMed/NCBI

219 

Xu X, Qiu Y, Chen S, Wang S, Yang R, Liu B, Li Y, Deng J, Su Y, Lin Z, et al: Different roles of the insulin-like growth factor (IGF) axis in non-small cell lung cancer. Curr Pharm Des. 28:2052–2064. 2022. View Article : Google Scholar : PubMed/NCBI

220 

Remsing Rix LL, Sumi NJ, Hu Q, Desai B, Bryant AT, Li X, Welsh EA, Fang B, Kinose F, Kuenzi BM, et al: IGF-binding proteins secreted by cancer-associated fibroblasts induce context-dependent drug sensitization of lung cancer cells. Sci Signal. 15:eabj58792022. View Article : Google Scholar : PubMed/NCBI

221 

Jiang S, Xu Z, Shi Y, Liang S, Jiang X, Xiao M, Wang K and Ding L: Circulating insulin-like growth factor-1 and risk of lung diseases: A Mendelian randomization analysis. Front Endocrinol (Lausanne). 14:11263972023. View Article : Google Scholar : PubMed/NCBI

222 

Xu J, Bie F, Wang Y, Chen X, Yan T and Du J: Prognostic value of IGF-1R in lung cancer: A PRISMA-compliant meta-analysis. Medicine (Baltimore). 98:e154672019. View Article : Google Scholar : PubMed/NCBI

223 

Wang Z, Li W, Guo Q, Wang Y, Ma L and Zhang X: Insulin-like growth factor-1 signaling in lung development and inflammatory lung diseases. Biomed Res Int. 2018:60575892018.PubMed/NCBI

224 

Peng Y and Tan J: The relationship between IGF pathway and acquired resistance to tyrosine kinase inhibitors in cancer therapy. Front Biosci (Landmark Ed). 28:1632023. View Article : Google Scholar : PubMed/NCBI

225 

Pal S, Yadav P, Sainis KB and Shankar BS: TNF-α and IGF-1 differentially modulate ionizing radiation responses of lung cancer cell lines. Cytokine. 101:89–98. 2018. View Article : Google Scholar : PubMed/NCBI

226 

Sun L, Yuan W, Wen G, Yu B, Xu F, Gan X, Tang J, Zeng Q, Zhu L, Chen C and Zhang W: Parthenolide inhibits human lung cancer cell growth by modulating the IGF-1R/PI3K/Akt signaling pathway. Oncol Rep. 44:1184–1193. 2020. View Article : Google Scholar : PubMed/NCBI

227 

Das D, Xie L and Hong J: Next-generation EGFR tyrosine kinase inhibitors to overcome C797S mutation in non-small cell lung cancer (2019–2024). RSC Med Chem. 15:3371–3394. 2024. View Article : Google Scholar : PubMed/NCBI

228 

Das D, Wang J and Hong J: Next-generation kinase inhibitors targeting specific biomarkers in non-small cell lung cancer (NSCLC): A recent overview. ChemMedChem. 16:2459–2479. 2021. View Article : Google Scholar : PubMed/NCBI

229 

Wang N, Zhang Y, Mi Y, Deng H, Chen G, Tang Z, Mao J, Cui S, Zhang Y and Wang L: Osimertinib for EGFR-mutant lung cancer with central nervous system metastases: A meta-analysis and systematic review. Ann Palliat Med. 9:3038–3047. 2020. View Article : Google Scholar : PubMed/NCBI

230 

Solomon BJ, Besse B, Bauer TM, Felip E, Soo RA, Camidge DR, Chiari R, Bearz A, Lin CC, Gadgeel SM, et al: Lorlatinib in patients with ALK-positive non-small-cell lung cancer: Results from a global phase 2 study. Lancet Oncol. 19:1654–1667. 2018. View Article : Google Scholar : PubMed/NCBI

231 

Soejima K, Yasuda H and Hirano T: Osimertinib for EGFR T790M mutation-positive non-small cell lung cancer. Expert Rev Clin Pharmacol. 10:31–38. 2017. View Article : Google Scholar : PubMed/NCBI

232 

Yang JCH, Ahn MJ, Kim DW, Ramalingam SS, Sequist LV, Su WC, Kim SW, Kim JH, Planchard D, Felip E, et al: Osimertinib in pretreated T790M-positive advanced non-small-cell lung cancer: AURA study phase II extension component. J Clin Oncol. 35:1288–1296. 2017. View Article : Google Scholar : PubMed/NCBI

233 

Ramalingam SS, Yang JCH, Lee CK, Kurata T, Kim DW, John T, Nogami N, Ohe Y, Mann H, Rukazenkov Y, et al: Osimertinib as first-line treatment of EGFR mutation-positive advanced non-small-cell lung cancer. J Clin Oncol. 36:841–849. 2018. View Article : Google Scholar : PubMed/NCBI

234 

Araki T, Kanda S, Horinouchi H and Ohe Y: Current treatment strategies for EGFR-mutated non-small cell lung cancer: From first line to beyond osimertinib resistance. Jpn J Clin Oncol. 53:547–561. 2023. View Article : Google Scholar : PubMed/NCBI

235 

Jänne PA, Planchard D, Kobayashi K, Cheng Y, Lee CK, Valdiviezo N, Laktionov K, Yang TY, Yu Y, Kato T, et al: CNS efficacy of osimertinib with or without chemotherapy in epidermal growth factor receptor-mutated advanced non-small-cell lung cancer. J Clin Oncol. 42:808–820. 2024. View Article : Google Scholar : PubMed/NCBI

236 

Ye Z and Guo J: Acquired ALK G1202R-, ALK I1171N-, or EML4-ALK-mediated resistance to ensartinib in lung adenocarcinoma but responded to lorlatinib: A case report. Front Oncol. 13:10821152023. View Article : Google Scholar : PubMed/NCBI

237 

Solomon BJ, Bauer TM, Mok TSK, Liu G, Mazieres J, de Marinis F, Goto Y, Kim DW, Wu YL, Jassem J, et al: Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: Updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 11:354–366. 2023. View Article : Google Scholar : PubMed/NCBI

238 

Bauer TM, Shaw AT, Johnson ML, Navarro A, Gainor JF, Thurm H, Pithavala YK, Abbattista A, Peltz G and Felip E: Brain penetration of lorlatinib: cumulative incidences of CNS and non-CNS progression with lorlatinib in patients with previously treated ALK-positive non-small-cell lung cancer. Target Oncol. 15:55–65. 2020. View Article : Google Scholar : PubMed/NCBI

239 

Rybarczyk-Kasiuchnicz A, Ramlau R and Stencel K: Treatment of brain metastases of non-small cell lung carcinoma. Int J Mol Sci. 22:5932021. View Article : Google Scholar : PubMed/NCBI

240 

Ernani V and Stinchcombe TE: Management of brain metastases in non-small-cell lung cancer. J Oncol Pract. 15:563–570. 2019. View Article : Google Scholar : PubMed/NCBI

241 

Lin JJ, Choudhury NJ, Yoda S, Zhu VW, Johnson TW, Sakhtemani R, Dagogo-Jack I, Digumarthy SR, Lee C, Do A, et al: Spectrum of mechanisms of resistance to crizotinib and lorlatinib in ROS1 fusion-positive lung cancer. Clin Cancer Res. 27:2899–2909. 2021. View Article : Google Scholar : PubMed/NCBI

242 

Corvaja C, Passaro A, Attili I, Aliaga PT, Spitaleri G, Signore ED and de Marinis F: Advancements in fourth-generation EGFR TKIs in EGFR-mutant NSCLC: Bridging biological insights and therapeutic development. Cancer Treat Rev. 130:1028242024. View Article : Google Scholar : PubMed/NCBI

243 

Desai A and Peters S: Immunotherapy-based combinations in metastatic NSCLC. Cancer Treat Rev. 116:1025452023. View Article : Google Scholar : PubMed/NCBI

244 

Passaro A, Jänne PA and Peters S: Antibody-drug conjugates in lung cancer: Recent advances and implementing strategies. J Clin Oncol. 41:3747–3761. 2023. View Article : Google Scholar : PubMed/NCBI

245 

Desai A, Abdayem P, Adjei AA and Planchard D: Antibody-drug conjugates: A promising novel therapeutic approach in lung cancer. Lung Cancer. 163:96–106. 2022. View Article : Google Scholar : PubMed/NCBI

246 

Merle G, Friedlaender A, Desai A and Addeo A: Antibody drug conjugates in lung cancer. Cancer J. 28:429–435. 2022. View Article : Google Scholar : PubMed/NCBI

247 

Rosner S, Valdivia A, Hoe HJ, Murray JC, Levy B, Felip E and Solomon BJ: Antibody-drug conjugates for lung cancer: Payloads and progress. Am Soc Clin Oncol Educ Book. 43:e3899682023. View Article : Google Scholar : PubMed/NCBI

248 

Marks S and Naidoo J: Antibody drug conjugates in non-small cell lung cancer: An emerging therapeutic approach. Lung Cancer. 163:59–68. 2022. View Article : Google Scholar : PubMed/NCBI

249 

Tarantino P, Carmagnani Pestana R, Corti C, Modi S, Bardia A, Tolaney SM, Cortes J, Soria JC and Curigliano G: Antibody-drug conjugates: Smart chemotherapy delivery across tumor histologies. CA Cancer J Clin. 72:165–182. 2022.PubMed/NCBI

250 

Weng W, Meng T, Zhao Q, Shen Y, Fu G, Shi J, Zhang Y, Wang Z, Wang M, Pan R, et al: Antibody-exatecan conjugates with a novel self-immolative moiety overcome resistance in colon and lung cancer. Cancer Discov. 13:950–973. 2023. View Article : Google Scholar : PubMed/NCBI

251 

Verma S, Breadner D and Raphael J: ‘Targeting’ improved outcomes with antibody-drug conjugates in non-small cell lung cancer-an updated review. Curr Oncol. 30:4329–4350. 2023. View Article : Google Scholar : PubMed/NCBI

252 

Parisi C, Mahjoubi L, Gazzah A and Barlesi F: TROP-2 directed antibody-drug conjugates (ADCs): The revolution of smart drug delivery in advanced non-small cell lung cancer (NSCLC). Cancer Treat Rev. 118:1025722023. View Article : Google Scholar : PubMed/NCBI

253 

Peters S, Loi S, André F, Chandarlapaty S, Felip E, Finn SP, Jänne PA, Kerr KM, Munzone E, Passaro A, et al: Antibody-drug conjugates in lung and breast cancer: Current evidence and future directions-a position statement from the ETOP IBCSG partners foundation. Ann Oncol. 35:607–629. 2024. View Article : Google Scholar : PubMed/NCBI

254 

Ricciuti B, Lamberti G, Andrini E, Genova C, De Giglio A, Bianconi V, Sahebkar A, Chiari R and Pirro M: Antibody-drug conjugates for lung cancer in the era of personalized oncology. Semin Cancer Biol. 69:268–278. 2021. View Article : Google Scholar : PubMed/NCBI

255 

Pourjamal N, Yazdi N, Halme A, Joncour VL, Laakkonen P, Saharinen P, Joensuu H and Barok M: Comparison of trastuzumab emtansine, trastuzumab deruxtecan, and disitamab vedotin in a multiresistant HER2-positive breast cancer lung metastasis model. Clin Exp Metastasis. 41:91–102. 2024. View Article : Google Scholar : PubMed/NCBI

256 

Fu Z, Gao C, Xie J, Zhang C, Li S, Gu M and Shi C: Incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted antibody-drug conjugates: A systematic review and meta-analysis of randomized controlled trials. BMC Cancer. 23:9602023. View Article : Google Scholar : PubMed/NCBI

257 

Larsen ME, Lyu H and Liu B: HER3-targeted therapeutic antibodies and antibody-drug conjugates in non-small cell lung cancer refractory to EGFR-tyrosine kinase inhibitors. Chin Med J Pulm Crit Care Med. 1:11–17. 2023. View Article : Google Scholar : PubMed/NCBI

258 

Chen Q, Jia G, Zhang X and Ma W: Targeting HER3 to overcome EGFR TKI resistance in NSCLC. Front Immunol. 14:13320572024. View Article : Google Scholar : PubMed/NCBI

259 

Belluomini L, Avancini A, Sposito M, Milella M, Rossi A and Pilotto S: Antibody-drug conjugates (ADCs) targeting TROP-2 in lung cancer. Expert Opin Biol Ther. 23:1077–1087. 2023. View Article : Google Scholar : PubMed/NCBI

260 

Paz-Ares LG, Juan-Vidal O, Mountzios GS, Felip E, Reinmuth N, de Marinis F, Girard N, Patel VM, Takahama T, Owen SP, et al: Sacituzumab govitecan versus docetaxel for previously treated advanced or metastatic non-small cell lung cancer: The randomized, open-label phase III EVOKE-01 study. J Clin Oncol. 42:2860–2872. 2024. View Article : Google Scholar : PubMed/NCBI

261 

Kim YJ, Li W, Zhelev DV, Mellors JW, Dimitrov DS and Baek DS: Chimeric antigen receptor-T cells are effective against CEACAM5 expressing non-small cell lung cancer cells resistant to antibody-drug conjugates. Front Oncol. 13:11240392023. View Article : Google Scholar : PubMed/NCBI

262 

Zanchetta C, De Marchi L, Macerelli M, Pelizzari G, Costa J, Aprile G and Cortiula F: Antibody-drug conjugates in non-small cell lung cancer: state of the art and future perspectives. Int J Mol Sci. 26:2212024. View Article : Google Scholar : PubMed/NCBI

263 

Belluomini L, Sposito M, Avancini A, Insolda J, Milella M, Rossi A and Pilotto S: Unlocking new horizons in small-cell lung cancer treatment: The onset of antibody-drug conjugates. Cancers (Basel). 15:53682023. View Article : Google Scholar : PubMed/NCBI

264 

Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, et al: Efficacy and safety of rovalpituzumab tesirine compared with topotecan as second-line therapy in DLL3-high SCLC: Results from the phase 3 TAHOE study. J Thorac Oncol. 16:1547–1558. 2021. View Article : Google Scholar : PubMed/NCBI

265 

Owen DH, Giffin MJ, Bailis JM, Smit MAD, Carbone DP and He K: DLL3: An emerging target in small cell lung cancer. J Hematol Oncol. 12:612019. View Article : Google Scholar : PubMed/NCBI

266 

Morgensztern D, Besse B, Greillier L, Santana-Davila R, Ready N, Hann CL, Glisson BS, Farago AF, Dowlati A, Rudin CM, et al: Efficacy and safety of rovalpituzumab tesirine in third-line and beyond patients with DLL3-expressing, relapsed/refractory small-cell lung cancer: Results from the phase II TRINITY study. Clin Cancer Res. 25:6958–6966. 2019. View Article : Google Scholar : PubMed/NCBI

267 

Lashari BH, Vallatharasu Y, Kolandra L, Hamid M and Uprety D: Rovalpituzumab tesirine: A novel DLL3-targeting antibody-drug conjugate. Drugs R D. 18:255–258. 2018. View Article : Google Scholar : PubMed/NCBI

268 

Zhao C, Zhang R, Yang H, Gao Y, Zou Y and Zhang X: Antibody-drug conjugates for non-small cell lung cancer: Advantages and challenges in clinical translation. Biochem Pharmacol. 226:1163782024. View Article : Google Scholar : PubMed/NCBI

269 

Neupane N, Thapa S, Bhattarai A, Ahuja K, Schlam I, Mittal A, Tolaney SM and Tarantino P: Opportunities and challenges for a histology-agnostic utilization of trastuzumab deruxtecan. Curr Oncol Rep. 25:1467–1482. 2023. View Article : Google Scholar : PubMed/NCBI

270 

Desai A, Subbiah V, Roy-Chowdhuri S, Sheshadri A, Deshmukh S and Peters S: Association of antibody-drug conjugate (ADC) target expression and interstitial lung disease (ILD) in non-small-cell lung cancer (NSCLC): Association or causation or neither? Cancers (Basel). 16:37532024. View Article : Google Scholar : PubMed/NCBI

271 

Attili I, Passaro A, Pavan A, Conte P, De Marinis F and Bonanno L: Combination immunotherapy strategies in advanced non-small cell lung cancer (NSCLC): Does biological rationale meet clinical needs? Crit Rev Oncol Hematol. 119:30–39. 2017. View Article : Google Scholar : PubMed/NCBI

272 

Tagliamento M, Genova C, Rossi G, Coco S, Rijavec E, Dal Bello MG, Boccardo S, Grossi F and Alama A: Microtubule-targeting agents in the treatment of non-small cell lung cancer: Insights on new combination strategies and investigational compounds. Expert Opin Investig Drugs. 28:513–523. 2019. View Article : Google Scholar : PubMed/NCBI

273 

Girard N: New strategies and novel combinations in EGFR TKI-resistant non-small cell lung cancer. Curr Treat Options Oncol. 23:1626–1644. 2022. View Article : Google Scholar : PubMed/NCBI

274 

Wu YL, Guarneri V, Voon PJ, Lim BK, Yang JJ, Wislez M, Huang C, Liam CK, Mazieres J, Tho LM, et al: Tepotinib plus osimertinib in patients with EGFR-mutated non-small-cell lung cancer with MET amplification following progression on first-line osimertinib (INSIGHT 2): A multicentre, open-label, phase 2 trial. Lancet Oncol. 25:989–1002. 2024. View Article : Google Scholar : PubMed/NCBI

275 

Yoshida R, Saigi M, Tani T, Springer BF, Shibata H, Kitajima S, Mahadevan NR, Campisi M, Kim W, Kobayashi Y, et al: MET-induced CD73 restrains STING-mediated immunogenicity of EGFR-mutant lung cancer. Cancer Res. 82:4079–4092. 2022. View Article : Google Scholar : PubMed/NCBI

276 

Zhao S, Ma Y, Liu L, Fang J, Ma H, Feng G, Xie B, Zeng S, Chang J, Ren J, et al: Ningetinib plus gefitinib in EGFR-mutant non-small-cell lung cancer with MET and AXL dysregulations: A phase 1b clinical trial and biomarker analysis. Lung Cancer. 188:1074682024. View Article : Google Scholar : PubMed/NCBI

277 

Wang S, Liu C, Yang C, Jin Y, Cui Q, Wang D, Ge T, He G, Li W, Zhang G, et al: PI3K/AKT/mTOR and PD-1/CTLA-4/CD28 pathways as key targets of cancer immunotherapy (review). Oncol Lett. 28:5672024. View Article : Google Scholar : PubMed/NCBI

278 

Fu ZY, Huang Y, Lian LS, Huang HT, Zhan SF, Cai Y, Li JX and Liu XH: Potential of semen coicis in enhancing the anti-tumor effects of PD-1 inhibitor on A549 cell lines by blocking the PI3K-AKT-mTOR pathway. Clin Transl Oncol. 26:2250–2261. 2024. View Article : Google Scholar : PubMed/NCBI

279 

Li C, Tian C, Liu Y, Liang J, Zeng Y, Yang Q, Liu Y, Wu D, Wu J, Wang J, et al: Comprehensive profiling reveals distinct microenvironment and metabolism characterization of lung adenocarcinoma. Front Genet. 12:6198212021. View Article : Google Scholar : PubMed/NCBI

280 

Li Y, Tuerxun H and Zhao Y, Liu X, Li X, Wen S and Zhao Y: The new era of lung cancer therapy: Combining immunotherapy with ferroptosis. Crit Rev Oncol Hematol. 198:1043592024. View Article : Google Scholar : PubMed/NCBI

281 

Nair NU, Greninger P, Zhang X, Friedman AA, Amzallag A, Cortez E, Sahu AD, Lee JS, Dastur A, Egan RK, et al: A landscape of response to drug combinations in non-small cell lung cancer. Nat Commun. 14:38302023. View Article : Google Scholar : PubMed/NCBI

282 

Zheng H, Zeltsman M, Zauderer MG, Eguchi T, Vaghjiani RG and Adusumilli PS: Chemotherapy-induced immunomodulation in non-small-cell lung cancer: A rationale for combination chemoimmunotherapy. Immunotherapy. 9:913–927. 2017. View Article : Google Scholar : PubMed/NCBI

283 

Corke L and Sacher A: New strategies and combinations to improve outcomes in immunotherapy in metastatic non-small-cell lung cancer. Curr Oncol. 29:38–55. 2021. View Article : Google Scholar : PubMed/NCBI

284 

Casagrande GMS, Silva MO, Reis RM and Leal LF: Liquid biopsy for lung cancer: Up-to-date and perspectives for screening programs. Int J Mol Sci. 24:25052023. View Article : Google Scholar : PubMed/NCBI

285 

Pellini B and Chaudhuri AA: ctDNA monitoring for small cell lung cancer: Ready for prime time? Clin Cancer Res. 29:2176–2178. 2023. View Article : Google Scholar : PubMed/NCBI

286 

Pan Y, Zhang JT, Gao X, Chen ZY, Yan B, Tan PX, Yang XR, Gao W, Gong Y, Tian Z, et al: Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients. Cancer Cell. 41:1763–1773 .e4. 2023.

287 

Sun X, Abrahamson P, Ballew N, Kalilani L, Phiri K, Bell KF, Slowley A, Zajac M, Hofstatter E, Stojadinovic A, et al: The utility of ctDNA in lung cancer clinical research and practice: A systematic review and meta-analysis of clinical studies. Cancer Invest. 41:571–592. 2023. View Article : Google Scholar : PubMed/NCBI

288 

Ren F, Fei Q, Qiu K, Zhang Y, Zhang H and Sun L: Liquid biopsy techniques and lung cancer: Diagnosis, monitoring and evaluation. J Exp Clin Cancer Res. 43:962024. View Article : Google Scholar : PubMed/NCBI

289 

Sands J, Li Q and Hornberger J: Urine circulating-tumor DNA (ctDNA) detection of acquired EGFR T790M mutation in non-small-cell lung cancer: An outcomes and total cost-of-care analysis. Lung Cancer. 110:19–25. 2017. View Article : Google Scholar : PubMed/NCBI

290 

Chen K, Yang F, Shen H, Wang C, Li X, Chervova O, Wu S, Qiu F, Peng D, Zhu X, et al: Individualized tumor-informed circulating tumor DNA analysis for postoperative monitoring of non-small cell lung cancer. Cancer Cell. 41:1749–1762.e6. 2023. View Article : Google Scholar : PubMed/NCBI

291 

Yan X and Liu C: Clinical application and prospect of MRD evaluation in lung cancer based on ctDNA level: A review. Tumori. 109:356–362. 2023. View Article : Google Scholar : PubMed/NCBI

292 

Chae YK and Oh MS: Detection of minimal residual disease using ctDNA in lung cancer: Current evidence and future directions. J Thorac Oncol. 14:16–24. 2019. View Article : Google Scholar : PubMed/NCBI

293 

Reina C, Šabanović B, Lazzari C, Gregorc V and Heeschen C: Unlocking the future of cancer diagnosis-promises and challenges of ctDNA-based liquid biopsies in non-small cell lung cancer. Transl Res. 272:41–53. 2024. View Article : Google Scholar : PubMed/NCBI

294 

Medford AJ, Moy B, Spring LM, Hurvitz SA, Turner NC and Bardia A: Molecular residual disease in breast cancer: Detection and therapeutic interception. Clin Cancer Res. 29:4540–4548. 2023. View Article : Google Scholar : PubMed/NCBI

295 

Lavacchi D, Gelmini S, Calabri A, Rossi G, Simi L, Caliman E, Mancini I, Salvianti F, Petroni G, Guidolin A, et al: Early changes in circulating tumor DNA (ctDNA) predict treatment response in metastatic KRAS-mutated colorectal cancer (mCRC) patients. Heliyon. 9:e218532023. View Article : Google Scholar : PubMed/NCBI

296 

Pellini B and Chaudhuri AA: Circulating tumor DNA minimal residual disease detection of non-small-cell lung cancer treated with curative intent. J Clin Oncol. 40:567–575. 2022. View Article : Google Scholar : PubMed/NCBI

297 

Dong S, Wang Z, Zhang JT, Yan B, Zhang C, Gao X, Sun H, Li YS, Yan HH, Tu HY, et al: Circulating tumor DNA-guided de-escalation targeted therapy for advanced non-small cell lung cancer: A nonrandomized controlled trial. JAMA Oncol. 10:932–940. 2024. View Article : Google Scholar : PubMed/NCBI

298 

Yao H, Wen L, Li Z and Xia C: Analysis of diagnostic value of CTC and CTDNA in early lung cancer. Cell Mol Biol (Noisy-le-grand). 69:57–62. 2023. View Article : Google Scholar

299 

Xie J, Hu B, Gong Y, He S, Lin J, Huang Q and Cheng J: A comparative study on ctDNA and tumor DNA mutations in lung cancer and benign cases with a high number of CTCs and CTECs. J Transl Med. 21:8732023. View Article : Google Scholar : PubMed/NCBI

300 

Xiang Y, Liu X, Wang Y, Zheng D, Meng Q, Jiang L, Yang S, Zhang S, Zhang X, Liu Y and Wang B: Mechanisms of resistance to targeted therapy and immunotherapy in non-small cell lung cancer: Promising strategies to overcoming challenges. Front Immunol. 15:13662602024. View Article : Google Scholar : PubMed/NCBI

301 

Zhang KR, Zhang YF, Lei HM, Tang YB, Ma CS, Lv QM, Wang SY, Lu LM, Shen Y, Chen HZ and Zhu L: Targeting AKR1B1 inhibits glutathione de novo synthesis to overcome acquired resistance to EGFR-targeted therapy in lung cancer. Sci Transl Med. 13:eabg64282021. View Article : Google Scholar : PubMed/NCBI

302 

Roys A, Chang X, Liu Y, Xu X, Wu Y and Zuo D: Resistance mechanisms and potent-targeted therapies of ROS1-positive lung cancer. Cancer Chemother Pharmacol. 84:679–688. 2019. View Article : Google Scholar : PubMed/NCBI

303 

Liu WJ, Du Y, Wen R, Yang M and Xu J: Drug resistance to targeted therapeutic strategies in non-small cell lung cancer. Pharmacol Ther. 206:1074382020. View Article : Google Scholar : PubMed/NCBI

304 

Lim ZF and Ma PC: Emerging insights of tumor heterogeneity and drug resistance mechanisms in lung cancer targeted therapy. J Hematol Oncol. 12:1342019. View Article : Google Scholar : PubMed/NCBI

305 

Meyer ML, Fitzgerald BG, Paz-Ares L, Cappuzzo F, Jänne PA, Peters S and Hirsch FR: New promises and challenges in the treatment of advanced non-small-cell lung cancer. Lancet. 404:803–822. 2024. View Article : Google Scholar : PubMed/NCBI

306 

Koga T, Suda K and Mitsudomi T: Utility of the Ba/F3 cell system for exploring on-target mechanisms of resistance to targeted therapies for lung cancer. Cancer Sci. 113:815–827. 2022. View Article : Google Scholar : PubMed/NCBI

307 

Makarem M and Jänne PA: Top advances of the year: Targeted therapy for lung cancer. Cancer. 130:3239–3250. 2024. View Article : Google Scholar : PubMed/NCBI

308 

Li S, Wang A, Wu Y, He S, Shuai W, Zhao M, Zhu Y, Hu X, Luo Y and Wang G: Targeted therapy for non-small-cell lung cancer: New insights into regulated cell death combined with immunotherapy. Immunol Rev. 321:300–334. 2024. View Article : Google Scholar : PubMed/NCBI

309 

Zullo L, Dall'Olio FG, Rossi G, Dellepiane C, Barletta G, Bennicelli E, Ingaliso M, Tagliamento M and Genova C: Molecular and genetic advances in small cell lung cancer landscape: From homogeneity to diversity. Int J Mol Sci. 25:2242023. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tao Z, Shao W, Zhou H, Xia S, Zeng J, Ren J, Wang X and Zhu H: Role of signaling pathways in lung cancer development and advances in targeted therapies (Review). Oncol Lett 30: 589, 2025.
APA
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J. ... Zhu, H. (2025). Role of signaling pathways in lung cancer development and advances in targeted therapies (Review). Oncology Letters, 30, 589. https://doi.org/10.3892/ol.2025.15335
MLA
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J., Wang, X., Zhu, H."Role of signaling pathways in lung cancer development and advances in targeted therapies (Review)". Oncology Letters 30.6 (2025): 589.
Chicago
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J., Wang, X., Zhu, H."Role of signaling pathways in lung cancer development and advances in targeted therapies (Review)". Oncology Letters 30, no. 6 (2025): 589. https://doi.org/10.3892/ol.2025.15335
Copy and paste a formatted citation
x
Spandidos Publications style
Tao Z, Shao W, Zhou H, Xia S, Zeng J, Ren J, Wang X and Zhu H: Role of signaling pathways in lung cancer development and advances in targeted therapies (Review). Oncol Lett 30: 589, 2025.
APA
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J. ... Zhu, H. (2025). Role of signaling pathways in lung cancer development and advances in targeted therapies (Review). Oncology Letters, 30, 589. https://doi.org/10.3892/ol.2025.15335
MLA
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J., Wang, X., Zhu, H."Role of signaling pathways in lung cancer development and advances in targeted therapies (Review)". Oncology Letters 30.6 (2025): 589.
Chicago
Tao, Z., Shao, W., Zhou, H., Xia, S., Zeng, J., Ren, J., Wang, X., Zhu, H."Role of signaling pathways in lung cancer development and advances in targeted therapies (Review)". Oncology Letters 30, no. 6 (2025): 589. https://doi.org/10.3892/ol.2025.15335
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team