Treatment of Lung Adenocarcinoma by Molecular-targeted Therapy and Immunotherapy

Overview

Journal Surg Today

Specialty General Surgery

Date 2017 Mar 11

PMID 28280984

Citations 64

Authors

Motonobu Saito

Hiroyuki Suzuki

Koji Kono

Seiichi Takenoshita

Takashi Kohno

Affiliations

Soon will be listed here.

Abstract

Lung adenocarcinoma (LADC) is a cancer treatable using targeted therapies against driver gene aberrations. EGFR mutations and ALK fusions are frequent gene aberrations in LADC, and personalized therapies against those aberrations have become a standard therapy. These targeted therapies have shown significant positive efficacy and tolerable toxicity compared to conventional chemotherapy, so it is necessary to identify additional druggable genetic aberrations. Other than EGFR mutations and ALK fusions, mutations in KRAS, HER2, and BRAF, and driver fusions involving RET and ROS1, have also been identified in LADC. Interestingly, the frequency of driver gene aberrations differs according to ethnicity, sex, and smoking, which leads to differences in treatment efficacy. To date, several molecular-targeted drugs against driver genes have been developed, and several clinical trials have been conducted to evaluate the efficacy. However, targeted therapies against driver-gene-negative cases have not yet been well developed. Efforts to identify a new druggable target for such cases are currently underway. Furthermore, immune checkpoint blockade therapy might be effective for driver-negative cases, especially those with accumulated mutations.

Citing Articles

Ethnic disparities in survival and progression among EGFR-mutated adenocarcinoma of lung cancer patients treated with tyrosine kinase inhibitors: a systematic review and meta-analysis.

de Moraes F, Rodrigues A, Pasqualotto E, Cassemiro J, Choque J, Burbano R Clin Transl Oncol. 2025; .

PMID: 39797945 DOI: 10.1007/s12094-024-03843-4.

Lin C, Lin K, Lin X, Yuan H, Zhang Y, Xie Z Transl Lung Cancer Res. 2024; 13(10):2713-2728.

PMID: 39507021 PMC: 11535849. DOI: 10.21037/tlcr-24-627.

Disulfidptosis-related gene predicts prognosis and indicates tumor immune infiltration in lung adenocarcinoma.

Zhu J, Ge H, Chen Y, Zhang S, Wu J, Nai W Transl Cancer Res. 2024; 13(9):5064-5072.

PMID: 39430814 PMC: 11483469. DOI: 10.21037/tcr-24-1182.

The progress of tumor vaccines clinical trials in non-small cell lung cancer.

Wang X, Niu Y, Bian F Clin Transl Oncol. 2024; .

PMID: 39179939 DOI: 10.1007/s12094-024-03678-z.

Cost-effectiveness Analysis of the Oncomine™ Dx Target Test MultiCDx System Using Next-generation Sequencing and Single-gene Test in Advanced and Recurrent Nonsquamous Non-small-cell Lung Cancer.

Kohara T, Ikeda S, Ishikawa K JMA J. 2024; 7(3):375-386.

PMID: 39114611 PMC: 11301018. DOI: 10.31662/jmaj.2023-0206.

References

Borghaei H, Paz-Ares L, Horn L, Spigel D, Steins M, Ready N . Nivolumab versus Docetaxel in Advanced Nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med. 2015; 373(17):1627-39. PMC: 5705936. DOI: 10.1056/NEJMoa1507643. View

Suzuki A, Mimaki S, Yamane Y, Kawase A, Matsushima K, Suzuki M . Identification and characterization of cancer mutations in Japanese lung adenocarcinoma without sequencing of normal tissue counterparts. PLoS One. 2013; 8(9):e73484. PMC: 3772023. DOI: 10.1371/journal.pone.0073484. View

Kim K, Roberts C . Targeting EZH2 in cancer. Nat Med. 2016; 22(2):128-34. PMC: 4918227. DOI: 10.1038/nm.4036. View

Wilson B, Roberts C . SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 2011; 11(7):481-92. DOI: 10.1038/nrc3068. View

Imielinski M, Berger A, Hammerman P, Hernandez B, Pugh T, Hodis E . Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell. 2012; 150(6):1107-20. PMC: 3557932. DOI: 10.1016/j.cell.2012.08.029. View

Gainor J, Dardaei L, Yoda S, Friboulet L, Leshchiner I, Katayama R . Molecular Mechanisms of Resistance to First- and Second-Generation ALK Inhibitors in ALK-Rearranged Lung Cancer. Cancer Discov. 2016; 6(10):1118-1133. PMC: 5050111. DOI: 10.1158/2159-8290.CD-16-0596. View

Kohno T, Nakaoku T, Tsuta K, Tsuchihara K, Matsumoto S, Yoh K . Beyond ALK-RET, ROS1 and other oncogene fusions in lung cancer. Transl Lung Cancer Res. 2015; 4(2):156-64. PMC: 4384213. DOI: 10.3978/j.issn.2218-6751.2014.11.11. View

Minuti G, DIncecco A, Cappuzzo F . Targeted therapy for NSCLC with driver mutations. Expert Opin Biol Ther. 2013; 13(10):1401-12. DOI: 10.1517/14712598.2013.827657. View

Tumeh P, Harview C, Yearley J, Shintaku I, Taylor E, Robert L . PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014; 515(7528):568-71. PMC: 4246418. DOI: 10.1038/nature13954. View

10.

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

11.

Topalian S, Hodi F, Brahmer J, Gettinger S, Smith D, Mcdermott D . Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012; 366(26):2443-54. PMC: 3544539. DOI: 10.1056/NEJMoa1200690. View

12.

Kadara H, Choi M, Zhang J, Parra E, Rodriguez-Canales J, Gaffney S . Whole-exome sequencing and immune profiling of early-stage lung adenocarcinoma with fully annotated clinical follow-up. Ann Oncol. 2016; 28(1):75-82. PMC: 5982809. DOI: 10.1093/annonc/mdw436. View

13.

Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L . ARID1A Deficiency Impairs the DNA Damage Checkpoint and Sensitizes Cells to PARP Inhibitors. Cancer Discov. 2015; 5(7):752-67. PMC: 4497871. DOI: 10.1158/2159-8290.CD-14-0849. View

14.

Nakaoku T, Tsuta K, Ichikawa H, Shiraishi K, Sakamoto H, Enari M . Druggable oncogene fusions in invasive mucinous lung adenocarcinoma. Clin Cancer Res. 2014; 20(12):3087-93. PMC: 6329293. DOI: 10.1158/1078-0432.CCR-14-0107. View

15.

Takeuchi K, Soda M, Togashi Y, Suzuki R, Sakata S, Hatano S . RET, ROS1 and ALK fusions in lung cancer. Nat Med. 2012; 18(3):378-81. DOI: 10.1038/nm.2658. View

16.

Hirsch F, Suda K, Wiens J, Bunn Jr P . New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016; 388(10048):1012-24. DOI: 10.1016/S0140-6736(16)31473-8. View

17.

Vaishnavi A, Capelletti M, Le A, Kako S, Butaney M, Ercan D . Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer. Nat Med. 2013; 19(11):1469-1472. PMC: 3823836. DOI: 10.1038/nm.3352. View

18.

Tan C, Gilligan D, Pacey S . Treatment approaches for EGFR-inhibitor-resistant patients with non-small-cell lung cancer. Lancet Oncol. 2015; 16(9):e447-e459. DOI: 10.1016/S1470-2045(15)00246-6. View

19.

Seki Y, Fujiwara Y, Kohno T, Takai E, Sunami K, Goto Y . Picoliter-Droplet Digital Polymerase Chain Reaction-Based Analysis of Cell-Free Plasma DNA to Assess EGFR Mutations in Lung Adenocarcinoma That Confer Resistance to Tyrosine-Kinase Inhibitors. Oncologist. 2016; 21(2):156-64. PMC: 4746084. DOI: 10.1634/theoncologist.2015-0288. View

20.

Oike T, Ogiwara H, Tominaga Y, Ito K, Ando O, Tsuta K . A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1. Cancer Res. 2013; 73(17):5508-18. DOI: 10.1158/0008-5472.CAN-12-4593. View