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This review analyzes core signaling mechanisms underlying CRC pathogenesis, highlighting genomic, epigenomic, and microbial features and their links to neoplastic evolution. It also surveys targeted and immune therapies, discusses key exploitable nodes within oncogenic pathways, and considers integrating AI to improve therapeutic targeting precision and patient stratification.",{"@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/signaling-pathways-involved-in-colorectal-cancer-pathogenesis-and-targeted-therapy-review-article/332574/",{"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/signaling-pathways-involved-in-colorectal-cancer-pathogenesis-and-targeted-therapy-review-article/332574.png","ImageObject",300,407,{"name":92,"@type":93},"Riley","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Which major signaling pathways are implicated in colorectal cancer pathogenesis?","Question",{"text":112,"@type":113},"Key pathways include Wnt/β-catenin, RAS/RAF/MEK/ERK, PI3K/AKT, and TGF-β circuits, which are often dysregulated by genetic mutations such as APC, KRAS, and PIK3CA.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do targeted therapies for metastatic colorectal cancer work, and what limits their effectiveness?",{"text":117,"@type":113},"EGFR inhibitors like cetuximab and panitumumab are used in metastatic CRC, but their efficacy is often reduced by intrinsic or acquired resistance mechanisms.",{"name":119,"@type":110,"acceptedAnswer":120},"What role do multi-omics and AI play in advancing personalized colorectal cancer treatment?",{"text":121,"@type":113},"Multi-omics integrates genomic, transcriptomic, proteomic, and metabolomic data to tailor therapies to a patient’s tumor profile. The review further emphasizes integrating AI to enhance precision of therapeutic targeting and patient stratification for personalized medicine.","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},332574,1790852831,{"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":24,"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},1374391975076,"https://ap-avatar.wpscdn.com/avatar/14000253ca4ec9f6853?x-image-process=image/resize,m_fixed,w_180,h_180&k=1783305029341752051","Signal Transduction [and Targeted Therapy](and Targeted Therapy www.nature.com/sigtrans)[ www.nature.com/sigtrans](and Targeted Therapy www.nature.com/sigtrans)  \nREVIEW ARTICLE  \nOPEN  \nSignaling pathways involved in colorectal cancer: pathogenesis and targeted therapy  \nQing Li 1,2,3, Shan Geng4, Hao Luo3,5, Wei Wang6, Ya-Qi Mo2, Qing Luo3, Lu Wang2, Guan-Bin Song3 ✉ , Jian-Peng Sheng7 ✉ and Bo Xu2 ✉  \n\n|  | Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Its complexity is influenced by various signal transduction networks that govern cellular proliferation, survival, differentiation, and apoptosis. The pathogenesis of CRC is a testament to the dysregulation of these signaling cascades, which culminates in the malignant transformation of colonic epithelium. This review aims to dissect the foundational signaling mechanisms implicated in CRC, to elucidate the generalized principles underpinning neoplastic evolution and progression. We discuss the molecular hallmarks of CRC, including the genomic, epigenomic and microbial features of CRC to highlight the role of signal transduction in the orchestration of the tumorigenic process. Concurrently, we review the advent of targeted and immune therapies in CRC, assessing their impact on the current clinical landscape. The development of these therapies has been informed by a deepening understanding of oncogenic signaling, leading to the identification of key nodes within these networks that can be exploited pharmacologically. Furthermore, we explore the potential of integrating AI to enhance the precision of therapeutic targeting and patient stratification, emphasizing their role in personalized medicine. In summary, our review captures the dynamic interplay between aberrant signaling in CRC pathogenesis and the concerted efforts to counteract these changes through targeted therapeutic strategies, ultimately aiming to pave the way |  |  |  |\n| --- | --- | --- | --- | --- |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n|  |  |  |  |  |\n| for improved prognosis |  | and personalized treatment modalities in | colorectal cancer. |  |\n|  | Signal Transduction and | Targeted Therapy (2024)9:266 | ; [https://doi.org/10.1038/s41392-024-01953-7](https://doi.org/10.1038/s41392-024-01953-7) |  |\n|  |  |  |  |  |\n\nINTRODUCTION  \nColorectal cancer (CRC) is a formidable global health adversary, consistently ranking as the third most prevalent and second most lethal malignancy worldwide.1 The disease claims more than 900,000 lives annually, with its incidence demonstrating a worrying ascendancy in populations traditionally considered at lower risk.2 This epidemiological burden underscores an urgent need for a nuanced understanding of CRC’s pathophysiology and the development of innovative therapeutic strategies.  \nAt the core of CRC’s pathogenesis lie aberrant signaling pathways that drive tumorigenesis, sustain cancer cell proliferation, and enable metastatic dissemination.3 These pathways, which include the Wnt/β-catenin, RAS/RAF/MEK/ERK, phosphoinositide 3-kinase (PI3K)/AKT, and transforming growth factor-beta (TGF-β) circuits, among others, are often dysregulated by a confluence of genetic mutations (means somatic variants or germline variants), such as adenomatous polyposis coli (APC), kirsten rat sarcoma viral oncogene homolog (KRAS), and PIK3CA.4 The intricate network of signaling cascades they form dictates not only the malignant phenotype but also the immune response and the tumor microenvironment (TME), influencing the efficacy of therapeutic interventions.  \nThe landscape of targeted therapy has evolved apace, as our molecular insight into CRC has deepened. Inhibitors of epidermal growth factor receptor (EGFR), such as cetuximab and panitumumab, have become stalwarts in the management of metastatic CRC, albe","cbCair2ebBELt356","https://ap.wps.com/l/cbCair2ebBELt356","pdf",5198594,48,"English","# Introduction\n# Global Epidemiology of CRC","[{\"question\":\"Which major signaling pathways are implicated in colorectal cancer pathogenesis?\",\"answer\":\"Key pathways include Wnt/β-catenin, RAS/RAF/MEK/ERK, PI3K/AKT, and TGF-β circuits, which are often dysregulated by genetic mutations such as APC, KRAS, and PIK3CA.\"},{\"question\":\"How do targeted therapies for metastatic colorectal cancer work, and what limits their effectiveness?\",\"answer\":\"EGFR inhibitors like cetuximab and panitumumab are used in metastatic CRC, but their efficacy is often reduced by intrinsic or acquired resistance mechanisms.\"},{\"question\":\"What role do multi-omics and AI play in advancing personalized colorectal cancer treatment?\",\"answer\":\"Multi-omics integrates genomic, transcriptomic, proteomic, and metabolomic data to tailor therapies to a patient’s tumor profile. The review further emphasizes integrating AI to enhance precision of therapeutic targeting and patient stratification for personalized medicine.\"}]","Signaling pathways involved in colorectal cancer - pathogenesis and targeted therapy - review article | PDF",1789998771,121]