[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-367565-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-367565-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","oncogenic-stress-response-mechanisms-as-new-therapeutic-targets-in-cancer-treatment-a-review","Oncogenic stress response mechanisms as new therapeutic targets in cancer treatment - A review","","Activation of oncogenes, such as through KRAS mutations, disrupts cellular homeostasis and triggers coordinated stress-response pathways that help cells withstand challenges during tumorigenesis. These responses promote adaptation and survival via heat shock proteins, the ubiquitin-proteasome system, autophagy, NRF2-ARE signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules. The review focuses on KRAS-driven transformation and highlights how targeting key regulators within these defense mechanisms may undermine cancer cell survival, improving existing therapies and enabling new treatment strategies.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/oncogenic-stress-response-mechanisms-as-new-therapeutic-targets-in-cancer-treatment-a-review/367565/",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/oncogenic-stress-response-mechanisms-as-new-therapeutic-targets-in-cancer-treatment-a-review/367565.png","ImageObject",300,407,{"name":42,"@type":43},"Bintang","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",15,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"How do KRAS-driven oncogenic signals trigger stress responses in cancer cells?","Question",{"text":63,"@type":64},"KRAS activation disrupts cellular homeostasis and initiates cascades of defense programs that include heat shock proteins, the ubiquitin-proteasome system, autophagy, NRF2-ARE signaling, and other stress-response regulators.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What major molecular components are highlighted as parts of the oncogenic stress response?",{"text":68,"@type":64},"Key components include heat shock proteins (HSPs), UPS, autophagy, NRF2–ARE signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules.",{"name":70,"@type":61,"acceptedAnswer":71},"Why are oncogenic stress response pathways promising therapeutic targets?",{"text":72,"@type":64},"Because the same pathways that allow cancer cells to adapt to oncogenic stress also control survival; selectively targeting pivotal regulators can potentially disrupt these mechanisms and enhance treatment effectiveness.","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},367565,1790253111,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",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":107,"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":113},962085564381,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","®  \n Narrative Review   \nOncogenic stress response mechanisms as new therapeutic targets in cancer treatment A review  \nJuan Iovanna, MD, PhDa ,b ,c ,* , Matías Estaras, PhDa , Daniel Grasso, PhDd , Martin E. Fernández Zapico, MDe , Jose Luis Neira, PhDf,g , Patricia Santofimia-Castaño, PhDa  \n\n| Abstract\u003Cbr>Activation of oncogenes, such as through mutations in Kirsten rat sarcoma viral oncogene homolog (KRAS), triggers profound disruptions in cellular homeostasis that set off a cascade of stress responses. These responses enable cells to cope with the array of challenges encountered during tumorigenesis by activating defense mechanisms that promote adaptation and survival. Key components of this oncogenic stress response include heat shock proteins, the ubiquitin-proteasome system, autophagy, nuclear factor erythroid 2-related factor 2–antioxidant response element signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules. This review concentrates on KRAS-driven oncogenic transformation, as KRAS mutations are among the most common in human cancers, accounting for over 90% of pancreatic ductal adenocarcinoma cases, around 30% of lung cancers, and approximately 50% of colorectal cancers. We examine the intricate molecular interplay between oncogenic stress and the associated cellular defense mechanisms, emphasizing the key molecular events that follow KRAS activation. Importantly, the very pathways that allow cancer cells to adapt to oncogenic stress also offer novel therapeutic opportunities. By selectively targeting pivotal regulators within these stress response pathways, we can potentially disrupt the survival mechanisms of cancer cells. This strategy not only promises to enhance the effectiveness of existing treatments but also paves the way for the development of innovative therapies designed to combat tumor progression. In essence, exploiting oncogenic stress responses represents an original and promising therapeutic approach in the fight against cancer. |\n| --- |\n| Abbreviations: ARE = antioxidant response element, ATM = ataxia-telangiectasia mutated, ATR = ataxia-telangiectasia and Rad3-related, DDR = DNA damage response, IDR = intrinsically disordered regions, LLPS = liquid-liquid phase separation, NHEJ = nonhomologous end-joining, NRF2 = nuclear factor erythroid 2-related factor 2, PDAC = pancreatic ductal adenocarcinomas, PIP3 = phosphatidylinositol (3,4,5)-trisphosphate, ROS = reactive oxygen species, UPS = ubiquitin-proteasome system. |\n| Keywords: autophagy, DDR, HSP, NRF2-ARE, p53, redox-regulating proteins, stress granules, UPS |\n\n1. Introduction  \n1.1. Oncogene activation  \nOncogenes, originally normal cellular genes known as protooncogenes, play crucial roles in maintaining cellular homeostasis[1] and cellular processes such as cell growth and division. The transition from proto-oncogene to oncogene can involve several mechanisms, including point mutations, gene amplification, or chromosomal translocations. [2] The conversion from  \nThis work was supported by INCa (grant number 2018-078), Canceropole PACA, and INSERM.  \nThe authors have no conflicts of interest to disclose.  \nThe datasets generated during and/or analyzed during the current study are publicly available.  \nThis study is a narrative literature review based exclusively on previously published data. It does not involve human participants, animals, or identifiable personal data. Therefore, approval from an ethics committee or institutional review board was not required.  \na Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Marseille, France, b Hospital de Alta Complejidad El Cruce, Florencio Varela, Argentina, c University Arturo Jauretche, Florencio Varela, Argentina, d Facultad de Farmaciay Bioquímica, Instituto de Estudios de la Inmunidad Humoral (IDEHU), Universidad de Buenos Aires, Buenos Aires, Argentina, e Division of ","cbCaij20E1msiotE","https://ap.wps.com/l/cbCaij20E1msiotE","pdf",1165835,12,"English","# Introduction\n## Oncogene activation\n## Oncogenic stress responses and therapeutic opportunities","[{\"question\":\"How do KRAS-driven oncogenic signals trigger stress responses in cancer cells?\",\"answer\":\"KRAS activation disrupts cellular homeostasis and initiates cascades of defense programs that include heat shock proteins, the ubiquitin-proteasome system, autophagy, NRF2-ARE signaling, and other stress-response regulators.\"},{\"question\":\"What major molecular components are highlighted as parts of the oncogenic stress response?\",\"answer\":\"Key components include heat shock proteins (HSPs), UPS, autophagy, NRF2–ARE signaling, DNA damage response proteins, p53, redox-regulating proteins, and stress granules.\"},{\"question\":\"Why are oncogenic stress response pathways promising therapeutic targets?\",\"answer\":\"Because the same pathways that allow cancer cells to adapt to oncogenic stress also control survival; selectively targeting pivotal regulators can potentially disrupt these mechanisms and enhance treatment effectiveness.\"}]","Oncogenic stress response mechanisms as new therapeutic targets in cancer treatment - A review | PDF",1790171408]