Current Therapy and Development of Therapeutic Agents for Lung Cancer

Overview

Journal Cell Insight

Specialty Biomedical Engineering

Date 2023 May 16

PMID 37193130

Authors

Zilai Wang

Jiyeon Kim

Pin Zhang

Jazmin M Galvan Achi

Yuwei Jiang

Lijun Rong

Affiliations

Soon will be listed here.

Abstract

In the past decades, great progress has been made for the prevention and treatment of lung cancer. Yet, lung cancer remains as the leading cause of cancer death worldwide. In this manuscript, we describe the current genetic and molecular characterization of lung cancer subtypes, review up-to-date treatment options for lung cancer patients, summarize the antibodies and small molecule drugs under clinical development, and elaborate on the expression and characteristics of important RTK primary targets and representative preclinical agents which may provide new opportunities for lung cancer treatment. Since gefitinib was first introduced to non-small-cell lung carcinoma (NSCLC) patients in 2002, remarkable progress has been made in targeted therapy for NSCLC patients with the development of multiple generations of small molecule inhibitors targeting relevant driver mutations. However, very little achievement has been made in the development of targeted drugs for small-cell lung carcinoma (SCLC). The successful harness of immune checkpoint inhibitors against PD-1/PD-L1 has marked a major advancement in recent lung cancer treatment. Looking forward, therapeutic strategies that tackle brain metastasis are highly desirable, the combination of molecular testing and strategies tailored to tackle tumor heterogeneity and resistance mechanisms is the key direction for future development.

Citing Articles

Precision epitope editing: A path to advanced immunotherapies.

Ji R, Wang M, Zhang Y Cell Insight. 2025; 4(2):100226.

PMID: 39906754 PMC: 11791281. DOI: 10.1016/j.cellin.2024.100226.

Experience and Care Pathway of Patients with Lung Cancer: An Online International Survey.

Frank P, Laurent J, Dallas L, Varriale P, Ciupek A Oncol Ther. 2024; 13(1):145-164.

PMID: 39699799 PMC: 11880444. DOI: 10.1007/s40487-024-00314-2.

PD-1-mediated inhibition of T cell activation: Mechanisms and strategies for cancer combination immunotherapy.

Liu R, Li H, Li S Cell Insight. 2024; 3(2):100146.

PMID: 38425643 PMC: 10901852. DOI: 10.1016/j.cellin.2024.100146.

PD-1 signaling negatively regulates the common cytokine receptor γ chain via MARCH5-mediated ubiquitination and degradation to suppress anti-tumor immunity.

Liu R, Zeng L, Li H, Shi J, Zhong B, Shu H Cell Res. 2023; 33(12):923-939.

PMID: 37932447 PMC: 10709454. DOI: 10.1038/s41422-023-00890-4.

Tumor suppressor PTEN regulation by tobacco smoke in lung squamous-cell carcinoma based on bioinformatics analysis.

Pustylnyak V, Alekseenok E, Perevalova A, Kozlov V, Gulyaeva L Heliyon. 2023; 9(8):e19044.

PMID: 37609416 PMC: 10440530. DOI: 10.1016/j.heliyon.2023.e19044.

References

Sun S, Schiller J, Gazdar A . Lung cancer in never smokers--a different disease. Nat Rev Cancer. 2007; 7(10):778-90. DOI: 10.1038/nrc2190. View

Socinski M, Jotte R, Cappuzzo F, Orlandi F, Stroyakovskiy D, Nogami N . Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018; 378(24):2288-2301. DOI: 10.1056/NEJMoa1716948. View

Nagasaka M, Zhu V, Lim S, Greco M, Wu F, Ou S . Beyond Osimertinib: The Development of Third-Generation EGFR Tyrosine Kinase Inhibitors For Advanced EGFR+ NSCLC. J Thorac Oncol. 2020; 16(5):740-763. DOI: 10.1016/j.jtho.2020.11.028. View

Wang S, Zimmermann S, Parikh K, Mansfield A, Adjei A . Current Diagnosis and Management of Small-Cell Lung Cancer. Mayo Clin Proc. 2019; 94(8):1599-1622. DOI: 10.1016/j.mayocp.2019.01.034. View

Zheng M . Classification and Pathology of Lung Cancer. Surg Oncol Clin N Am. 2016; 25(3):447-68. DOI: 10.1016/j.soc.2016.02.003. View

Shepherd F, Pereira J, Ciuleanu T, Tan E, Hirsh V, Thongprasert S . Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med. 2005; 353(2):123-32. DOI: 10.1056/NEJMoa050753. View

Schreiber R, Old L, Smyth M . Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science. 2011; 331(6024):1565-70. DOI: 10.1126/science.1203486. View

Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M . Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007; 357(7):664-72. DOI: 10.1056/NEJMoa071780. View

Akhurst T . Staging of Non-Small-Cell Lung Cancer. PET Clin. 2017; 13(1):1-10. DOI: 10.1016/j.cpet.2017.09.004. View

10.

Vinay D, Ryan E, Pawelec G, Talib W, Stagg J, Elkord E . Immune evasion in cancer: Mechanistic basis and therapeutic strategies. Semin Cancer Biol. 2015; 35 Suppl:S185-S198. DOI: 10.1016/j.semcancer.2015.03.004. View

11.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

12.

Abel S, Hasan S, Horne Z, Colonias A, Wegner R . Stereotactic body radiation therapy in early-stage NSCLC: historical review, contemporary evidence and future implications. Lung Cancer Manag. 2019; 8(1):LMT09. PMC: 6488937. DOI: 10.2217/lmt-2018-0013. View

13.

Cross D, Ashton S, Ghiorghiu S, Eberlein C, Nebhan C, Spitzler P . AZD9291, an irreversible EGFR TKI, overcomes T790M-mediated resistance to EGFR inhibitors in lung cancer. Cancer Discov. 2014; 4(9):1046-61. PMC: 4315625. DOI: 10.1158/2159-8290.CD-14-0337. View

14.

Gay C, Stewart C, Park E, Diao L, Groves S, Heeke S . Patterns of transcription factor programs and immune pathway activation define four major subtypes of SCLC with distinct therapeutic vulnerabilities. Cancer Cell. 2021; 39(3):346-360.e7. PMC: 8143037. DOI: 10.1016/j.ccell.2020.12.014. View

15.

Katayama R, Lovly C, Shaw A . Therapeutic targeting of anaplastic lymphoma kinase in lung cancer: a paradigm for precision cancer medicine. Clin Cancer Res. 2015; 21(10):2227-35. PMC: 4435823. DOI: 10.1158/1078-0432.CCR-14-2791. View

16.

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

17.

Vallieres E, Shepherd F, Crowley J, Van Houtte P, Postmus P, Carney D . The IASLC Lung Cancer Staging Project: proposals regarding the relevance of TNM in the pathologic staging of small cell lung cancer in the forthcoming (seventh) edition of the TNM classification for lung cancer. J Thorac Oncol. 2009; 4(9):1049-59. DOI: 10.1097/JTO.0b013e3181b27799. View

18.

Malhotra J, Malvezzi M, Negri E, La Vecchia C, Boffetta P . Risk factors for lung cancer worldwide. Eur Respir J. 2016; 48(3):889-902. DOI: 10.1183/13993003.00359-2016. View

19.

Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015; 387(10027):1540-1550. DOI: 10.1016/S0140-6736(15)01281-7. View

20.

Relli V, Trerotola M, Guerra E, Alberti S . Abandoning the Notion of Non-Small Cell Lung Cancer. Trends Mol Med. 2019; 25(7):585-594. DOI: 10.1016/j.molmed.2019.04.012. View