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This review consolidates recent advances in clinicopathological features, targeted drug development, resistance mechanisms, and emerging therapeutic targets for EML4-ALK-positive NSCLC.",{"@graph":14,"@context":72},[15,34,55],{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/eml4-alk-in-non-small-cell-lung-cancer-molecular-mechanisms-and-targeted-therapies/357333/",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/eml4-alk-in-non-small-cell-lung-cancer-molecular-mechanisms-and-targeted-therapies/357333.png","ImageObject",300,407,{"name":42,"@type":43},"Aldword","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":33},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"Why is EML4-ALK considered a pivotal target in NSCLC?","Question",{"text":62,"@type":63},"EML4-ALK is a fusion gene that drives aberrant proliferation and is central to NSCLC pathogenesis. It is also implicated in oncogenic signaling, supporting precision-medicine-based treatment strategies.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"What challenges arise even though ALK inhibitors are effective for EML4-ALK-positive tumors?",{"text":67,"@type":63},"Drug resistance remains a major challenge, causing intrinsic or acquired failure to sustain desired clinical responses. This variability makes durable outcomes difficult for some patients.",{"name":69,"@type":60,"acceptedAnswer":70},"How are EML4-ALK fusions commonly detected in patients?",{"text":71,"@type":63},"Clinical detection methods include RT-PCR, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). 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Advances in molecular biology and targeted therapeutic agents have ushered NSCLC into the era of precision medicine. The echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene represents a pivotal target for personalized treatment in NSCLC. Although ALK inhibitors exhibit significant efficacy against EML4-ALK-positive tumors, addressing drug resistance remains a major challenge. Identifying novel therapeutic targets and implementing combination therapies are essential for optimizing subsequent treatment strategies and improving overall prognosis. In the management of patients with EML4-ALK gene fusion, continuous monitoring of tumor progression and timely adjustment of treatment regimens based on disease status are critical to achieving long-term clinical benefits. This review comprehensively summarizes recent advances in the clinicopathological features, targeted drug development, resistance mechanisms, and potential therapeutic targets associated with the EML4-ALK fusion gene.  \nKeywords  \nnon-small cell lung cancer(NSCLC), EML4-ALK fusion gene, clinicopathological characteristics, drug resistance mechanisms, therapeutic targets  \nReceived: 12 November 2025; Revised: 24 April 2026; Accepted: 22 May 2026  \n1. Introduction  \nLung cancer is the leading cause of cancer-related mortality worldwide and represents the most commonly diagnosed cancer in China.1 It is broadly classified into small cell lung cancer and non-small cell lung cancer (NSCLC), with NSCLC accounting for approximately 85% of all cases and constituting the predominant histological subtype.2 Key driveroncogenesin NSCLC include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), and Rat sarcoma (RAS) genes.3 The ALK gene can form fusion proteins with various partners, driving aberrant tumor cell proliferation and playing a critical role inNSCLC pathogenesis. Patients withALK fusion-positive lung cancer generally demonstrate superior survival outcomes and a wider array of therapeutic options compared to those with other driver mutations, leading to the  \n1Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China 2Department of Oncology, The General Hospital of Western Theater Command, Chengdu, Sichuan, China  \nCorresponding authors:  \nDaijun Zhou, PhD, Department of Oncology, The General Hospital of Western Theater Command, No. 270, Rongdu Avenue, Chengdu 610083, Sichuan, China.  \nEmail: [daijunzhou@vip.qq.com](daijunzhou@vip.qq.com)  \nDong Li, PhD, Department of Oncology, the General Hospital of Western Theater Command, No. 270, Rongdu Avenue, Chengdu 610083, Sichuan, China.  \nEmail: [1](13438078785@163.com)[3438078785@163.com](13438078785@163.com)  \nCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons  \nAttribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)).  \ncolloq","cbCaivSyL4onPonp","https://ap.wps.com/l/cbCaivSyL4onPonp","pdf",2087348,16,"English","# Introduction\n## EML4-ALK as a key driver in NSCLC\n## Detecting EML4-ALK fusions in clinical practice\n## ALK-targeted therapy and the resistance problem\n## Scope of the review","[{\"question\":\"Why is EML4-ALK considered a pivotal target in NSCLC?\",\"answer\":\"EML4-ALK is a fusion gene that drives aberrant proliferation and is central to NSCLC pathogenesis. It is also implicated in oncogenic signaling, supporting precision-medicine-based treatment strategies.\"},{\"question\":\"What challenges arise even though ALK inhibitors are effective for EML4-ALK-positive tumors?\",\"answer\":\"Drug resistance remains a major challenge, causing intrinsic or acquired failure to sustain desired clinical responses. This variability makes durable outcomes difficult for some patients.\"},{\"question\":\"How are EML4-ALK fusions commonly detected in patients?\",\"answer\":\"Clinical detection methods include RT-PCR, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). These approaches support molecular profiling to guide targeted therapy.\"}]","EML4-ALK in Non-small Cell Lung Cancer: Molecular Mechanisms and Targeted Therapies | PDF",1790129646]