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

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 in TNBC 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.