The Biology and Management of Non-small Cell Lung Cancer

Overview

Journal Nature

Specialty Science

Date 2018 Jan 25

PMID 29364287

Citations 2123

Authors

Roy S Herbst

Daniel Morgensztern

Chris Boshoff

Affiliations

Soon will be listed here.

Abstract

Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.

Citing Articles

TIMM23 overexpression drives NSCLC cell growth and survival by enhancing mitochondrial function.

Zha J, Li J, Yin H, Shen M, Xia Y Cell Death Dis. 2025; 16(1):174.

PMID: 40082395 PMC: 11906786. DOI: 10.1038/s41419-025-07505-3.

Mediates Immunosuppression of the Tumor Microenvironment in Non-Small Cell Lung Cancer.

Fan Y, Ji X, Yuan K, Wu Q, Lou M J Inflamm Res. 2025; 18:3333-3347.

PMID: 40078575 PMC: 11900795. DOI: 10.2147/JIR.S509316.

Distribution of and Mutations in Patients with Surgically Resected Non-Small Cell Lung Cancer from Southern Italy: Real-Life Data from a Single Institution and Literature Review.

Piazzolla M, Parente P, Centra F, Fabrizio F, Delcuratolo M, Centonza A Cancers (Basel). 2025; 17(5).

PMID: 40075579 PMC: 11899559. DOI: 10.3390/cancers17050730.

Robust vs. Non-robust radiomic features: the quest for optimal machine learning models using phantom and clinical studies.

Hosseini S, Hajianfar G, Hall B, Servaes S, Rosa-Neto P, Ghafarian P Cancer Imaging. 2025; 25(1):33.

PMID: 40075547 PMC: 11905451. DOI: 10.1186/s40644-025-00857-1.

Glycyrrhizin enhances the antitumor activity of cisplatin in non‑small cell lung cancer cells by influencing DNA damage and apoptosis.

Tong Z, Wang Z, Jiang J, Fu W, Hu S Oncol Lett. 2025; 29(4):207.

PMID: 40070780 PMC: 11894513. DOI: 10.3892/ol.2025.14954.

References

Uchibori K, Inase N, Araki M, Kamada M, Sato S, Okuno Y . Brigatinib combined with anti-EGFR antibody overcomes osimertinib resistance in EGFR-mutated non-small-cell lung cancer. Nat Commun. 2017; 8:14768. PMC: 5355811. DOI: 10.1038/ncomms14768. View

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

Herbst R, Soria J, Kowanetz M, Fine G, Hamid O, Gordon M . Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515(7528):563-7. PMC: 4836193. DOI: 10.1038/nature14011. View

Turke A, Zejnullahu K, Wu Y, Song Y, Dias-Santagata D, Lifshits E . Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010; 17(1):77-88. PMC: 2980857. DOI: 10.1016/j.ccr.2009.11.022. View

Curran M, Montalvo W, Yagita H, Allison J . PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010; 107(9):4275-80. PMC: 2840093. DOI: 10.1073/pnas.0915174107. View

Wu Y, Cheng Y, Zhou X, Lee K, Nakagawa K, Niho S . Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017; 18(11):1454-1466. DOI: 10.1016/S1470-2045(17)30608-3. 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

Zhang J, Fujimoto J, Zhang J, Wedge D, Song X, Zhang J . Intratumor heterogeneity in localized lung adenocarcinomas delineated by multiregion sequencing. Science. 2014; 346(6206):256-9. PMC: 4354858. DOI: 10.1126/science.1256930. View

Rikova K, Guo A, Zeng Q, Possemato A, Yu J, Haack H . Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell. 2007; 131(6):1190-203. DOI: 10.1016/j.cell.2007.11.025. View

10.

Reck M, Rabe K . Precision Diagnosis and Treatment for Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(9):849-861. DOI: 10.1056/NEJMra1703413. View

11.

Abbosh C, Birkbak N, Wilson G, Jamal-Hanjani M, Constantin T, Salari R . Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature. 2017; 545(7655):446-451. PMC: 5812436. DOI: 10.1038/nature22364. View

12.

Ahrendt S, Hu Y, Buta M, McDermott M, Benoit N, Yang S . p53 mutations and survival in stage I non-small-cell lung cancer: results of a prospective study. J Natl Cancer Inst. 2003; 95(13):961-70. DOI: 10.1093/jnci/95.13.961. View

13.

Kris M, Gaspar L, Chaft J, Kennedy E, Azzoli C, Ellis P . Adjuvant Systemic Therapy and Adjuvant Radiation Therapy for Stage I to IIIA Completely Resected Non-Small-Cell Lung Cancers: American Society of Clinical Oncology/Cancer Care Ontario Clinical Practice Guideline Update. J Clin Oncol. 2017; 35(25):2960-2974. DOI: 10.1200/JCO.2017.72.4401. View

14.

Lin J, Riely G, Shaw A . Targeting ALK: Precision Medicine Takes on Drug Resistance. Cancer Discov. 2017; 7(2):137-155. PMC: 5296241. DOI: 10.1158/2159-8290.CD-16-1123. View

15.

Scagliotti G, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C . Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol. 2008; 26(21):3543-51. DOI: 10.1200/JCO.2007.15.0375. View

16.

Maemondo M, Inoue A, Kobayashi K, Sugawara S, Oizumi S, Isobe H . Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med. 2010; 362(25):2380-8. DOI: 10.1056/NEJMoa0909530. View

17.

Voron T, Marcheteau E, Pernot S, Colussi O, Tartour E, Taieb J . Control of the immune response by pro-angiogenic factors. Front Oncol. 2014; 4:70. PMC: 3980099. DOI: 10.3389/fonc.2014.00070. View

18.

Facchinetti F, Rossi G, Bria E, Soria J, Besse B, Minari R . Oncogene addiction in non-small cell lung cancer: Focus on ROS1 inhibition. Cancer Treat Rev. 2017; 55:83-95. DOI: 10.1016/j.ctrv.2017.02.010. View

19.

Shaw A, Felip E, Bauer T, Besse B, Navarro A, Postel-Vinay S . Lorlatinib in non-small-cell lung cancer with ALK or ROS1 rearrangement: an international, multicentre, open-label, single-arm first-in-man phase 1 trial. Lancet Oncol. 2017; 18(12):1590-1599. PMC: 5777233. DOI: 10.1016/S1470-2045(17)30680-0. View

20.

Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard J . Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol. 2003; 21(12):2237-46. DOI: 10.1200/JCO.2003.10.038. View