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FOXM1-dependent transcriptional activity and downstream pathways coordinate responses to genotoxic and oxidative stress as well as mitotic catastrophe, including networks shaped by drug-induced toxicity and protein-protein interactions. Therapeutically targeting FOXM1 is proposed to trigger apoptosis in drug-resistant cancers, alongside key translational challenges.",{"@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/research-report/","Research & 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FOXM1 inhibitors could work against drug-resistant cancers?",{"text":71,"@type":63},"The document notes that FOXM1 inhibitors show strong synergy with traditional chemotherapies and targeted therapies, and that FOXM1 contributes to specific resistance such as venetoclax resistance via upregulation of BCL2A1.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},344852,1790293053,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & 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apoptosis in a variety of human cancers  \nSanjeev Raghuwanshi 1 and Andrei L. Gartel 1 ✉  \n© The Author(s) 2026  \n\n|  |  |  |\n| --- | --- | --- |\n|  | FOXM1 (forkhead box protein M1) is a member of the transcription factors (TF) in the forkhead (FOX) family. Numerous studies over the past several years have progressively contributed to our current understanding of FOXM1 functions. Early work characterized FOXM1 as a proliferation-associated mammalian TF that controls cell cycle-transcriptional program, and is essential for proper mitotic function and genomic stability in normal cells. However, FOXM1 is aberrantly high-expressed in the majority of human cancers. A large body of literature from different studies has demonstrated FOXM1 as a critical molecule that regulates multiple aspects of cancer cells and maintains all major cancer hallmarks. In addition, recent studies have documented FOXM1 in cancer therapy resistance. Indeed, FOXM1 is repeatedly identified as a common factor associated with the higher cancer stage and weaker response to cancer therapies by regulating several targets relevant to drug response and cell survival. FOXM1-dependent transcriptional activity and downstream pathways regulate multiple functions in response to drug-induced genotoxic stress, oxidative stress, and mitotic catastrophe. FOXM1 also interacts with other proteins, and these protein-protein interactions regulate different functions and signaling pathways in response to drug-induced toxicity. Here, we mainly review and discuss our current molecular understanding of the mechanisms through which FOXM1 in cancer cells executes these new roles, and thereby induces therapy resistance and inhibits apoptosis in a variety of human cancers. We also discuss the opportunity and challenges for |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | therapeutically targeting FOXM1 to induce apoptosis in drug-resistant cancers. |  |\n|  |  |  |\n|  |  |  |\n|  | Cell Death and Disease (2026)17:230; [https://doi.org/10.1038/s41419-025-08321-5](https://doi.org/10.1038/s41419-025-08321-5) |  |\n|  |  |  |\n\nFACTS  \n● FOXM1 is overexpressed in the majority of human cancers and contributes to all the hallmarks of cancer.  \n● FOXM1 is repeatedly identified as a common factor associated with higher cancer stage and weaker response to cancer therapies.  \n● The microarray and pathway analysis demonstrated that FOXM1 controls a wide variety of cellular processes in cancers via regulating a plethora of transcriptional targets in the network.  \n● FOXM1-dependent transcriptional activity and associated pathways induce therapy resistance and inhibit apoptosis in a variety of human cancers.  \n● FOXM1 regulates multiple functions in response to drug-induced genotoxic stress, oxidative stress, and mitotic catastrophe.  \n● FOXM1 contributes to venetoclax resistance, in part through the upregulation of BCL2A1, an anti-apoptotic member of the BCL2 family.  \n● FOXM1 inhibitors have great synergy with different traditional chemotherapies and targeted cancer therapies.  \nOPEN QUESTIONS  \n● Can small-molecule FOXM1 inhibitors be used clinically as anticancer treatment?  \n● Can FOXM1inhibitors be more effective in the clinic when used in combination with existing therapies?  \n● Is FOXM1 inhibition during short-term treatment toxic to normal, proliferating cell compartments of the adult?  \n● Why have FOXM1 inhibitors not yet entered clinical trials? Is there a need for more thorough preclinical studies on their anti-cancer efficacy?  \nINTRODUCTION  \nCancer is a heterogeneous group of more than 100 diseases characterized by the uncontrollable growth of abnormal cells with the potential to spread to other parts of the body. The cancer burden is rising worldwide. Based on current est","cbCaioGDlTpFHHqD","https://ap.wps.com/l/cbCaioGDlTpFHHqD","pdf",1144589,17,"English","# FACTS\n# OPEN QUESTIONS\n# INTRODUCTION","[{\"question\":\"What role does FOXM1 play in human cancers?\",\"answer\":\"FOXM1 is overexpressed in most human cancers and contributes to multiple cancer hallmarks by regulating broad transcriptional programs that sustain cancer cell functions.\"},{\"question\":\"How is FOXM1 linked to therapy resistance and apoptosis?\",\"answer\":\"FOXM1-dependent transcriptional activity and downstream pathways regulate responses to drug-induced genotoxic stress, oxidative stress, and mitotic catastrophe, promoting therapy resistance while inhibiting apoptosis.\"},{\"question\":\"What evidence suggests FOXM1 inhibitors could work against drug-resistant cancers?\",\"answer\":\"The document notes that FOXM1 inhibitors show strong synergy with traditional chemotherapies and targeted therapies, and that FOXM1 contributes to specific resistance such as venetoclax resistance via upregulation of BCL2A1.\"}]","FOXM1 induces therapy resistance and inhibits apoptosis in a variety of human cancers | PDF",1790055465,43]