Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer

Sep 24, 2026

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FOXM1 (Forkhead box M1) is an oncogenic transcription factor strongly upregulated in breast cancer and other cancers, driving tumorigenesis as well as growth and progression. It is present across all breast cancer subtypes and is linked to poor patient survival, particularly in triple negative breast cancer (TNBC). New strategies to inhibit FOXM1, including combination therapies using FOXM1 inhibitors with synergistic cancer drugs, may improve outcomes for all subtypes and suppress recurrent advanced ER- and HER2-positive tumors.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Abstract

Rationale for FOXM1 as a therapeutic target

FOXM1 inhibitors and combination therapy directions

Relevance to breast cancer subtypes and resistance

Katzenellenbogen etal. Breast Cancer Research (2023) 25:76 [https://doi.org/10.1186/s13058-023-01675-8](https://doi.org/10.1186/s13058-023-01675-8) Breast Cancer Research REVIEW Open Access Targeting the oncogenic transcription factor FOXM1 to improve outcomes in all subtypes of breast cancer Benita S. Katzenellenbogen 1,2,3*, Valeria Sanabria Guillen1 and John A. Katzenellenbogen2,4 Abstract FOXM1 (Forkhead box M1) is an oncogenic transcription factor that is greatly upregulated in breast cancer and many other cancers where it promotes tumorigenesis, and cancer growth and progression. It is expressed in all subtypes of breast cancer and is the factor most associated with risk of poor patient survival, especially so in triple negative breast cancer (TNBC) . Thus, new approaches to inhibiting FOXM1 and its activities, and combination therapies utilizing FOXM1 inhibitors in conjunction with known cancer drugs that work together synergistically, could improve cancer treatment outcomes. Targeting FOXM1 might prove especially beneficial inTNBC where few targeted therapies currently exist, and also in suppressing recurrent advanced estrogen receptor (ER)-positive and HER2-positive breast cancers for which treatments with ER or HER2 targeted therapies that were effective initially are no longer beneficial. We present these perspectives and future directions in the context of what is known about FOXM1, its regulation, and its key roles in promoting cancer aggressiveness and metastasis, while being absent or very low in most normal non-regenerating adult tissues. We discuss new inhibitors of FOXM1 and highlight FOXM1 as an attractive target for controlling drug-resistant and difficult-to-suppress breast cancers, and how blocking FOXM1 might improve outcomes for patients with all subtypes of breast cancer. Keywords FOXM1, Breast cancer, Inhibitors, Transcriptional activity, Drug resistance Breast cancer is highly heterogeneous but FOXM1 is expressed in all subtypes Breast cancer is the most common cancer in women worldwide, and its incidence has been increasing due to growth of the aging population [1], and emergent trends in lifestyle factors including obesity, physical inactivity, *Correspondence: Benita S. Katzenellenbogen [katzenel@illinois.edu](katzenel@illinois.edu) 1 Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 2 Cancer Center at Illinois, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA 3 Institute for Genomic Biology, University of Illinois at UrbanaChampaign, Urbana, IL 61801, USA 4 Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA and alcohol use [2]. The nature of the breast tumors also varies by ethnicity, with African American women having the highest rate of the most difficult to treat triple negative breast cancer (TNBC) subtype compared with other ethnic groups in the United States [3]. A major challenge in treating breast cancer effectively is the very heterogeneous nature of the disease, which encompasses a wide array of histological and molecular characteristics [1, 3, 4] that divides broadly into 6 intrinsic subtypes: Normal-like, Basal-like, Claudin-low, human epidermal growth factor 2 (HER2)-enriched, Luminal B, and Luminal A. While estrogen receptor (ER)-targeted and HER2-targeted therapies are subtypespecific, and are highly effective as first-line treatments [5–7], the efficacy of these therapies can change overtime, becoming less effective with treatment and disease © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, 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 changes were made. Th

FAQs

Why is FOXM1 considered oncogenic in breast cancer?

FOXM1 is a transcription factor that is greatly upregulated in breast cancer and promotes tumorigenesis, cancer growth, and progression.

How is FOXM1 related to patient outcomes across breast cancer subtypes?

FOXM1 is expressed in all breast cancer subtypes and is most associated with poor survival, especially in TNBC.

What treatment approach does the article propose for FOXM1?

It highlights inhibiting FOXM1 and using FOXM1 inhibitors in combination with existing cancer drugs to achieve synergistic improvements in therapy outcomes.

Sep 24, 2026

Uploaded by Callum