Lung Cancer Pathogenesis and Therapeutic Advances
DOI:
https://doi.org/10.62051/3p38v941Keywords:
Carcinogenesis, tobacco-specific nitrosamines, particulate matter, targeted therapy; Immune checkpoint inhibitors.Abstract
Lung cancer is the leading cause of cancer-related death globally, killing 1.8 million in 2020. In the US, its mortality exceeds that of prostate, breast and colorectal cancers. Tobacco and air particles drive it. China's male smoking rate and PM2.5 risks are examples. Regional disparities are huge, like in East Asia and Africa. Pathogenesis involves six core mechanisms: Tobacco carcinogen-induced DNA damage (85% population-attributable risk), PM2.5/radon genotoxicity, Somatic driver mutations (EGFR/KRAS), Occupational carcinogen exposure, Chronic pulmonary inflammation, and Lifestyle modulators. Early-stage surgery has good survival rates, but for advanced cases, new drugs are used. Global 5 - year survival is low. This review outlines etiologies, evaluates treatments and proposes strategies. This review delineates molecular etiologies, evaluates therapeutic innovations, and proposes multisectoral strategies to mitigate this escalating public health crisis.
Downloads
References
[1] Jemal A, Bray F, Center M M, et al. Global cancer statistics. CA: A Cancer Journal for Clinicians, 2011, 61(2): 69-90. DOI: https://doi.org/10.3322/caac.20107
[2] Chinese Center for Disease Control and Prevention. 2021 China Adult Tobacco Survey Report. People's Medical Publishing House, 2022.
[3] World Bank. The cost of air pollution: Strengthening the economic case for action. World Bank Group, 2020.
[4] Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. International Agency for Research on Cancer, 2020.
[5] Allemani C, Matsuda T, Di Carlo V, et al. Global surveillance of trends in cancer survival 2000–14 (CONCORD-3): Analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. The Lancet, 2018, 391(10125): 1023-1075. DOI: https://doi.org/10.1016/S0140-6736(17)33326-3
[6] U.S. Department of Health and Human Services. The health consequences of smoking—50 years of progress: A report of the Surgeon General. U.S. CDC, 2014.
[7] Peto R, Darby S, Deo H, et al. Smoking, smoking cessation, and lung cancer in the UK since 1950. Nature, 2000, 404(6780): 635–643.
[8] International Agency for Research on Cancer. Tobacco smoke and involuntary smoking (IARC Monographs Vol. 83). WHO Press, 2004.
[9] Loomis D, Grosse Y, Lauby-Secretan B, et al. The carcinogenicity of outdoor air pollution. The Lancet Oncology, 2013, 14(13): 1262–1263. DOI: https://doi.org/10.1016/S1470-2045(13)70487-X
[10] Pope C A III, Burnett R T, Thun M J, et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA, 2011, 287(9): 1132–1141. DOI: https://doi.org/10.1001/jama.287.9.1132
[11] Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: Collaborative analysis of individual data from 13 European case-control studies. BMJ, 2005, 330(7485): 223–226. DOI: https://doi.org/10.1136/bmj.38308.477650.63
[12] McKay J D, Hung R J, Han Y, et al. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes. Nature Genetics, 2017, 49(7): 1126–1132. DOI: https://doi.org/10.1038/ng.3892
[13] The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung adenocarcinoma. Nature, 2014, 511(7511): 543–550. DOI: https://doi.org/10.1038/nature13385
[14] Belinsky S A. Gene-promoter hypermethylation as a biomarker in lung cancer. Nature Reviews Cancer, 2005, 5(9): 707–717. DOI: https://doi.org/10.1038/nrc1432
[15] Stayner L, Kuempel E, Gilbert S, et al. An epidemiological study of the role of chrysotile asbestos fibre dimensions in determining respiratory disease risk in exposed workers. Occupational and Environmental Medicine, 2013, 65(10): 707–713.
[16] Straif K, Benbrahim-Tallaa L, Baan R, et al. A review of human carcinogens—Part C: Metals, arsenic, dusts, and fibres. The Lancet Oncology, 2009, 10(5): 453–454. DOI: https://doi.org/10.1016/S1470-2045(09)70134-2
[17] World Cancer Research Fund International. Diet, nutrition, physical activity and lung cancer. 2018.
[18] The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. New England Journal of Medicine, 1994, 330(15): 1029–1035. DOI: https://doi.org/10.1056/NEJM199404143301501
[19] Bagnardi V, Rota M, Botteri E, et al. Alcohol consumption and lung cancer risk in never smokers: A meta-analysis. Annals of Oncology, 2011, 22(12): 2631–2639. DOI: https://doi.org/10.1093/annonc/mdr027
[20] Durham A L, Adcock I M. The relationship between COPD and lung cancer. Lung Cancer, 2013, 90(2): 121–127. DOI: https://doi.org/10.1016/j.lungcan.2015.08.017
[21] Adeloye D, Chua S, Lee C, et al. Global and regional estimates of COPD prevalence: Systematic review and meta-analysis. Journal of Global Health, 2016, 5(2): 020415. DOI: https://doi.org/10.7189/jogh.05.020415
[22] Goldstraw P, Chansky K, Crowley J, et al. The IASLC lung cancer staging project: Proposals for revision of the TNM stage groupings in the forthcoming (eighth) edition of the TNM classification for lung cancer. Journal of Thoracic Oncology, 2016, 11(1): 39–51. DOI: https://doi.org/10.1016/j.jtho.2015.09.009
[23] Detterbeck F C, Lewis S Z, Diekemper R, et al. Executive summary: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest, 2017, 143(5 Suppl): 7S-37S. DOI: https://doi.org/10.1378/chest.12-2377
[24] Timmerman R, Paulus R, Galvin J, et al. Stereotactic body radiation therapy for inoperable early-stage lung cancer. JAMA, 2010, 303(11): 1070–1076. DOI: https://doi.org/10.1001/jama.2010.261
[25] Chang J Y, Verma V, Li M, et al. Proton beam radiotherapy and concurrent chemotherapy for unresectable stage III non-small cell lung cancer: Final results of a phase II study. Journal of Clinical Oncology, 2017, 35(5): 578–586.
[26] Schiller J H, Harrington D, Belani C P, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. New England Journal of Medicine, 2002, 346(2): 92–98. DOI: https://doi.org/10.1056/NEJMoa011954
[27] Scagliotti G V, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology, 2008, 26(21): 3543–3551. DOI: https://doi.org/10.1200/JCO.2007.15.0375
[28] Mok T S, Wu Y L, Ahn M J, et al. Osimertinib or platinum-pemetrexed in EGFR T790M-positive lung cancer. New England Journal of Medicine, 2017, 376(7): 629–640. DOI: https://doi.org/10.1056/NEJMoa1612674
[29] Shaw A T, Kim D W, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. New England Journal of Medicine, 2013, 368(25): 2385–2394. DOI: https://doi.org/10.1056/NEJMoa1214886
[30] Sandler A, Gray R, Perry M C, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. New England Journal of Medicine, 2006, 355(24): 2542–2550. DOI: https://doi.org/10.1056/NEJMoa061884
Downloads
Published
Issue
Section
License
Copyright (c) 2025 Transactions on Materials, Biotechnology and Life Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
