[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-354856-105":59,"doc-detail-354856-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","advances-in-targeting-kras-mutations-a-promising-approach-for-the-treatment-of-non-small-cell-lung-cancer-review","Advances in targeting KRAS mutations: A promising approach for the treatment of non-small cell lung cancer - Review","","KRAS mutations are among the most frequent oncogenic drivers, particularly in non-small cell lung cancer (NSCLC). Although KRAS was long considered “undruggable” due to structural features and lack of clear drug-binding sites, selective KRAS G12C inhibitors such as sotorasib and adagrasib, along with immunotherapy progress, show potential clinical activity. The review summarizes KRAS-targeted therapies and immunotherapies, highlighting signaling-network opportunities, limitations, resistance mechanisms, and the efficacy of rational combination regimens, while stressing ongoing needs for optimized combinations and resistance management.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/advances-in-targeting-kras-mutations-a-promising-approach-for-the-treatment-of-non-small-cell-lung-cancer-review/354856/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/advances-in-targeting-kras-mutations-a-promising-approach-for-the-treatment-of-non-small-cell-lung-cancer-review/354856.png","ImageObject",300,407,{"name":92,"@type":93},"Himbo","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why were KRAS mutations historically difficult to target in cancer therapy?","Question",{"text":112,"@type":113},"KRAS was considered “undruggable” because of the protein’s smooth molecular surface and the absence of obvious drug binding sites.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What developments changed the outlook for KRAS-targeted treatment in NSCLC?",{"text":117,"@type":113},"Selective KRAS G12C inhibitors (including sotorasib and adagrasib) and progress in immunotherapy have demonstrated potential clinical activity.",{"name":119,"@type":110,"acceptedAnswer":120},"What does the review cover regarding KRAS-targeted therapies?",{"text":121,"@type":113},"It reviews KRAS-targeted therapies and immunotherapies, including limitations, resistance mechanisms, and the efficacy of combination regimens.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},354856,1790207667,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":34,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},687197100911,"https://ap-avatar.wpscdn.com/avatar/a000239b6f1da00475?x-image-process=image/resize,m_fixed,w_180,h_180&k=1785132997149421697","ONCOLOGY REPORTS 55: 39, 2026  \nAdvances in targeting KRAS mutations: A promising approach for the treatment of non‑small cell lung cancer (Review)  \nUPESH SHARMA, JINCHENG SONG, HEMRAJ KANDU, YUE ZHU and ZHAOXIA DAI  \nDepartment of Medical Oncology, The Second Hospital of Dalian Medical University, Dalian, Liaoning 116021, P.R. China  \nReceived May 13, 2025; Accepted November 6, 2025  \nDOI: 10. 3892/or.2026.9044  \nAbstract. Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are among the most frequent oncogenicdrivers in cancer, particularly in non‑small cell lung cancer (NSCLC) . KRAS was previously considered an ‘undruggable’target due to the protein's smooth molecular surface and the absence of obvious drug binding sites. However, the develop‑ ment of selective KRAS G12C inhibitors, such as sotorasiband adagrasib, together with progress in immunotherapy, have demonstrated potential clinical activity. Further understanding of the complex signaling networks driven by KRAS has revealed new opportunities to target this pathway directly or through rational combination strategies. The present review explored KRAS‑targeted therapies and immunotherapies, including limitations, resistance mechanisms and the efficacy of combination regimens. Although there has been notable progress, concerns regarding optimal therapy combinations, resistance management and early treatment strategies remain. The present review demonstrated the need for continued research to address these challenges and improve outcomes for patients with KRAS‑mutated NSCLC.  \nContents  \n1. Introduction  \n2. KRAS signaling pathways  \n3. Clinical significance of KRAS mutations in NSCLC  \n4. Targeting KRAS mutations in NSCLC  \n5. Advances in treating KRAS mutations in NSCLC  \n6. Clinical impact of KRAS co‑mutations (STK11, TP53 and KEAP1)  \n7. Mechanisms of resistance to anti‑KRAS therapies  \nCorrespondence to: Professor Zhaoxia Dai, Department of Medical Oncology, The Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou, Dalian, Liaoning 116021, P.R. China  \nE‑mail: [dzx21882003@163.com](dzx21882003@163.com)  \nKey words: drug resistance, immunotherapy, KRAS mutation, non‑small cell lung cancer, targeted therapy  \n8. Future directions  \n9. Conclusion  \n1. Introduction  \nNon‑small cell lung cancer (NSCLC) is one of the leading causes of cancer‑related mortalities globally and accounts for ~85% of all lung cancer cases (1) . Among the molecular subtypes of NSCLC, Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are one of the most commonly identified oncogenic drivers. These mutations are commonly prevalent in lung adenocarcinoma (LUAD) and are strongly linked with smoking and environmental carcinogens (2) . KRAS is a member of the rat sarcoma viral (RAS) oncogene family and accounts for the majority of RAS‑related mutations encountered in human cancer. KRAS alterations account for~85% of all RAS mutations (3) . The prevalence of KRAS mutations varies across cancer types, with the highest frequen‑ cies found in pancreatic (88%), colorectal (45‑50%) and lung cancer (31‑35%) (4) . KRAS mutations are present in ~30% of LUAD cases in Western populations and ~10% of in Asian populations (5,6) .  \nThe KRAS proto‑oncogene encodes a small guanine triphosphate (GTPase) that acts as a binary switch in signal transductions of multiple receptor tyrosine kinases, such as mesenchymal‑epithelial transition (MET), epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), thus regulating cellular functions such as proliferation, differentiation and survival. KRAS is a clonal transforming oncogene and is a key oncogenic driver across multiple solid tumors (7‑9) .  \nStructurally, KRAS is a 21‑kDa GTPase composed of a conserved G‑domain and two dynamic regulatory regions, Switch I and Switch II, which control its active (GTP‑bound) and inactive (GDP‑bound) states. The Switch II pocket (SII‑P) forms the allosteric site targeted by K","cbCaitkT8rDWnQhp","https://ap.wps.com/l/cbCaitkT8rDWnQhp","pdf",1513365,14,"English","# Introduction\n# KRAS signaling pathways\n# Clinical significance of KRAS mutations in NSCLC\n# Targeting KRAS mutations in NSCLC\n# Advances in treating KRAS mutations in NSCLC\n# Clinical impact of KRAS co-mutations (STK11, TP53 and KEAP1)\n# Mechanisms of resistance to anti-KRAS therapies\n# Future directions\n# Conclusion","[{\"question\":\"Why were KRAS mutations historically difficult to target in cancer therapy?\",\"answer\":\"KRAS was considered “undruggable” because of the protein’s smooth molecular surface and the absence of obvious drug binding sites.\"},{\"question\":\"What developments changed the outlook for KRAS-targeted treatment in NSCLC?\",\"answer\":\"Selective KRAS G12C inhibitors (including sotorasib and adagrasib) and progress in immunotherapy have demonstrated potential clinical activity.\"},{\"question\":\"What does the review cover regarding KRAS-targeted therapies?\",\"answer\":\"It reviews KRAS-targeted therapies and immunotherapies, including limitations, resistance mechanisms, and the efficacy of combination regimens.\"}]","Advances in targeting KRAS mutations: A promising approach for the treatment of non-small cell lung cancer - Review | PDF",1790114452,35]