Targeting forkhead box M1 transcription factor in breast cancer

Breast cancer continues to be the most commonly diagnosed malignancy and second most common cause of cancer-related deaths among women in the United States. Improved understanding of the molecular heterogeneity of breast tumors and the approval of multiple targeted therapies have revolutionized the treatment landscape and long-term survival rates for patients with breast cancer. Despite the development of highly effective targeted agents, drug resistance and disease progression remain major clinical concerns. Improved understanding of the molecular mechanisms mediating drug resistance will allow new treatments to be developed. The forkhead box M1 (FoxM1) transcription factor is overexpressed in breast cancer and strongly associated with resistance to targeted therapies and chemotherapy. FoxM1 regulates all hallmarks of cancer, including proliferation, mitosis, EMT, invasion, and metastasis. Inhibition of FoxM1 transcription factor function is a potential strategy for overcoming breast cancer progression. In this research update, we review the role of FoxM1 in breast cancer and pharmacological approaches for blocking FoxM1 transcription factor function. Future preclinical studies should evaluate combination drug strategies to inhibit FoxM1 function and upstream kinase signaling pathways as potential strategies to treat resistant and metastatic breast cancers.