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Immunotherapy leverages the immune system, with advances including immune checkpoint inhibitors, monoclonal antibodies, antibody–drug conjugates, and bispecific antibodies. This review summarizes mechanisms of FDA-approved agents and evaluates factors that enhance or reduce immunotherapy efficacy, including emerging resistance. ",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/the-impact-of-genetic-mutations-on-the-efficacy-of-immunotherapies-in-lung-cancer/329496/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/the-impact-of-genetic-mutations-on-the-efficacy-of-immunotherapies-in-lung-cancer/329496.png","ImageObject",300,407,{"name":42,"@type":43},"Seraphina","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are genetic mutations central to lung cancer mortality?","Question",{"text":63,"@type":64},"Lung cancer mortality is largely driven by genetic mutations that promote tumor initiation and progression and enable immune escape and oncogenic signaling, making current interventions insufficient.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What major lung cancer types are discussed?",{"text":68,"@type":64},"The review distinguishes Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), noting differences in aggressiveness, survival rates, and associations such as smoking.",{"name":70,"@type":61,"acceptedAnswer":71},"How does immunotherapy address lung cancer and what determines its efficacy?",{"text":72,"@type":64},"Immunotherapy improves outcomes by harnessing the immune system through approaches like PD-1/PD-L1 checkpoint inhibitors, monoclonal antibodies, and related modalities. Its efficacy is shaped by both positive factors and mechanisms that generate or strengthen drug resistance and immune escape.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},329496,1790196468,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146,"preview_page_count":4},962075114101,"https://ap-avatar.wpscdn.com/avatar/e000253a75eb197efd?x-image-process=image/resize,m_fixed,w_180,h_180&k=1780044092746381165","Review  \nThe Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer  \nKi Lui 1,*, Kwok-Kuen Cheung 2, Winnie Wing-Man Ng 3, Yanping Wang 1, Doreen W. H. Au 1 and William C. Cho 4, *  \n1 Department of Health Sciences, School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong SAR, China; [ypwang@hkmu.edu.hk](ypwang@hkmu.edu.hk) (Y.W.); [dau@hkmu.edu.hk](dau@hkmu.edu.hk) (D.W.H.A.)  \n2 Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong SAR, China; [alexkk.cheung@polyu.edu.hk](alexkk.cheung@polyu.edu.hk)  \n3 School of Nursing, The Hong Kong Polytechnic University, Hong Kong SAR, China; [winnie.wm.ng@polyu.edu.hk](winnie.wm.ng@polyu.edu.hk)  \n4 Department of Clinical Oncology, Queen Elizabeth Hospital, Hong Kong SAR, China  \n* Correspondence: [aklui@hkmu.edu.hk](aklui@hkmu.edu.hk) (K.L.); [chocs@ha.org.hk](chocs@ha.org.hk) (W.C.C.)  \nCitation: Lui, K.; Cheung, K.-K.; Ng, W.W.-M.; Wang, Y.; Au, D.W.H.; Cho, W.C. The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer. Int. J. Mol. Sci. 2024, 25, 11954. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms252211954  \nAcademic Editor: Ilaria Marrocco  \nReceived: 10 October 2024  \nRevised: 28 October 2024  \nAccepted: 2 November 2024  \nPublished: 7 November 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nAbstract: Lung cancer is the leading cause of cancer-related mortality worldwide, primarily driven by genetic mutations. The most common genetic alterations implicated in lung cancer include mutations in TP53, KRAS, KEAP1, NF1, EGFR, NRF2, ATM, ALK, Rb1, BRAF, MET, and ERBB2 . Targeted therapies have been developed to inhibit cancer growth by focusing on these specific genetic mutations. However, either the mutations are undruggable or the efficacy of these therapies is often compromisedover time due to the emergence of drug resistance, which can occur through additional mutations in the targeted protein or alternative growth signaling pathways. In recent years, immunotherapy has emerged as a promising approach to enhance the effectiveness of cancer treatment by leveraging the body’s immune system. Notable advancements include immune checkpoint inhibitors, monoclonal antibodies targeting cell surface receptors, antibody–drug conjugates, and bispecific antibodies. This review provides an overview of the mechanisms of FDA-approved immunotherapeutic drugs, offering an updated perspective on the current state and future developments in lung cancer therapy. More importantly, the factors that positively and negatively impact the immunotherapy’s efficacy will also be discussed.  \nKeywords: chemoresistance; genetic mutation; immunotherapy; lung cancer  \n1. Introduction  \nThe International Agency for Research on Cancer (IARC), a specialized cancer agency of the World Health Organization (WHO), reports that lung cancer is the most lethal and the leading cause of death among all cancers. In 2022 alone, it is estimated to cause approximately 1.8 million deaths, accounting for 18.7% of all cancer-related deaths, and results in 2.5 million new diagnoses, representing 12.4% of all cancer cases globally [1] . These distressing statistics indicate that our current understanding and medical intervention for lung cancer are inadequate, requiring further efforts in combating this disease. Furthermore, statistical projections suggest that the global cancer burden is set to double by 2050 [1] . Consequently, the need for comprehensive cancer research to develop effective therapy is more critical than ever.  \nOver several decades dedicated to cancer resear","cbCaiikqIEJDgMlh","https://ap.wps.com/l/cbCaiikqIEJDgMlh","pdf",2473481,25,"English","# Introduction\n# Genetic Mutations in Lung Cancer and the Pathways to Drug Resistance","[{\"question\":\"Why are genetic mutations central to lung cancer mortality?\",\"answer\":\"Lung cancer mortality is largely driven by genetic mutations that promote tumor initiation and progression and enable immune escape and oncogenic signaling, making current interventions insufficient.\"},{\"question\":\"What major lung cancer types are discussed?\",\"answer\":\"The review distinguishes Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC), noting differences in aggressiveness, survival rates, and associations such as smoking.\"},{\"question\":\"How does immunotherapy address lung cancer and what determines its efficacy?\",\"answer\":\"Immunotherapy improves outcomes by harnessing the immune system through approaches like PD-1/PD-L1 checkpoint inhibitors, monoclonal antibodies, and related modalities. Its efficacy is shaped by both positive factors and mechanisms that generate or strengthen drug resistance and immune escape.\"}]","The Impact of Genetic Mutations on the Efficacy of Immunotherapies in Lung Cancer | PDF",1789984345,63]