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Evidence indicates testosterone can signal through canonical androgen receptor pathways and non-canonical, AR-related mechanisms that reshape membrane receptor signaling, metabolic programs, and the tumor immune microenvironment. These actions promote tumor growth, metastasis, stemness maintenance, and therapy resistance, while clinical investigations targeting testosterone/androgen signaling show therapeutic potential across multiple cancer contexts.",{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/testosterone-and-cancers-biological-functions-molecular-mechanisms-and-therapy/349393/",{"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/testosterone-and-cancers-biological-functions-molecular-mechanisms-and-therapy/349393.png","ImageObject",300,407,{"name":92,"@type":93},"Aldword","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-24","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"How does testosterone influence tumor development according to the review?","Question",{"text":112,"@type":113},"Testosterone can drive tumor growth and metastasis through both canonical androgen receptor signaling and non-canonical AR-related mechanisms affecting membrane signaling, metabolism, and the tumor immune microenvironment.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What roles are highlighted for testosterone at the tumor immune microenvironment level?",{"text":117,"@type":113},"The review describes testosterone as modulating the tumor immune microenvironment, which supports progression processes such as growth, stemness maintenance, and resistance to therapy.",{"name":119,"@type":110,"acceptedAnswer":120},"Which cancer contexts beyond prostate and breast cancer are emphasized?",{"text":121,"@type":113},"The review highlights hepatocellular carcinoma and cutaneous melanoma as additional contexts that broaden understanding of testosterone biology across cancers.","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},349393,1790270412,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":14,"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},2336478940917,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Zhou et al. Molecular Cancer (2026) 25:158 Molecular Cancer  \n[https://doi.org/10.1186/s12943-026-02676-9](https://doi.org/10.1186/s12943-026-02676-9)  \nREVIEW Open Access  \nTestosterone and cancers: biological   \nfunctions, molecular mechanisms and therapy  \nZhixiang Zhou1†, Tengda Huang1†, Jiaxin Li1,2†, Li Fu1, Lin Xu1, Xuping Feng1, Zheng Zhang1, Hongyuan Pan1, Ke Qin1, Xinyi Zhou1, Yan Xiang1 and Kefei Yuan1*  \nAbstract  \nTestosterone, the principal androgen in humans, plays an essential role in maintaining physiological homeostasis. In recent years, accumulating evidence has implicated testosterone in the progression of diverse malignancies, underscoring its context-dependent roles in tumor biology. A series of studies suggest that testosterone can act through canonical androgen receptor (AR) signaling as well as non-canonical, AR-related mechanisms to modulate membrane receptor-mediated signal transduction, metabolic reprogramming, and the tumor immune microenvironment, thereby fostering tumor growth, metastasis, maintenance of stemness, and the development of therapy resistance. Notably, interventional strategies targeting testosterone/androgen signaling have entered clinical investigation and have demonstrated therapeutic promise. Beyond the best-developed clinical paradigms of prostate and breast cancer, we also highlight hepatocellular carcinoma and cutaneous melanoma as informative additional contexts that broaden the understanding of testosterone biology across cancers. Here, we propose that testosterone is best understood not simply as a hormonal input into isolated cancer pathways, but as a systemslevel endocrine regulator of tumor plasticity that integrates transcriptional programs, rapid kinase signaling, and membrane receptor-associated responses across distinct tumor contexts. Within this framework, membrane androgen signaling is considered an emerging but still largely preclinical therapeutic vulnerability, whereas androgen-directed interventions in prostate and breast cancer represent the most clinically mature translational paradigms.  \nKeywords Testosterone, Androgen Receptor, Tumor Microenvironment, Oncogenic Pathway, Cancer Therapy  \n†Zhixiang Zhou, Tengda Huang and Jiaxin Li contributed equally to this work.  \n*Correspondence: Kefei Yuan[ykf13@163.com](ykf13@163.com)  \n1Department of General Surgery and Laboratory of Liver Surgery, Division of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China  \n2Department of General Surgery, Dafang County People’s Hospital, Bijie, Guizhou Province, China  \nIntroduction  \nCancer is a complex disease marked by the uncontrolled proliferation of abnormal cells that breach their natural boundaries, infiltrate surrounding tissues, and disseminate to distant organs [1–3]. Cancer remains one of the most pressing global health challenges, ranking as a leading cause of mortality worldwide [4]. According to the latest global estimates released by the World Health Organization (WHO) and the International Agency for Research on Cancer (IARC), approximately 19–20 million new cancer cases and around 10 million cancerrelated deaths occur each year worldwide [5]. Recent projections from the American Cancer Society further  \n© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the mater","cbCaieJZCOPEVge2","https://ap.wps.com/l/cbCaieJZCOPEVge2","pdf",2560629,25,"English","# Abstract\n# Introduction\n## Cancer burden and urgency\n## Testosterone biology and androgen signaling","[{\"question\":\"How does testosterone influence tumor development according to the review?\",\"answer\":\"Testosterone can drive tumor growth and metastasis through both canonical androgen receptor signaling and non-canonical AR-related mechanisms affecting membrane signaling, metabolism, and the tumor immune microenvironment.\"},{\"question\":\"What roles are highlighted for testosterone at the tumor immune microenvironment level?\",\"answer\":\"The review describes testosterone as modulating the tumor immune microenvironment, which supports progression processes such as growth, stemness maintenance, and resistance to therapy.\"},{\"question\":\"Which cancer contexts beyond prostate and breast cancer are emphasized?\",\"answer\":\"The review highlights hepatocellular carcinoma and cutaneous melanoma as additional contexts that broaden understanding of testosterone biology across cancers.\"}]","Testosterone and cancers - biological functions, molecular mechanisms and therapy | PDF",1790083119,63]