Therapeutic Landscape of FOXM1 in Triple-Negative Breast Cancer and Aggressive Solid Cancers

Area of Science:

• Oncology
• Molecular Biology
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER2 targets, characterized by heterogeneity, chemoresistance, metastasis, and poor survival.
• FOXM1, a transcription factor, promotes proliferation, invasion, metastasis, and drug resistance in aggressive cancers, including TNBC.
• TP53 mutations, prevalent in ~80% of TNBC cases, lead to FOXM1 overexpression, establishing FOXM1 as a critical therapeutic target.

Purpose of the Study:

• To review the role of FOXM1 in cancer progression, particularly in TNBC.
• To highlight the current landscape of FOXM1 inhibitor development for cancer therapy.

Main Methods:

• Literature review of studies on FOXM1 function in cancer.
• Analysis of existing research on FOXM1 inhibitors and their preclinical/clinical status.

Main Results:

• FOXM1 is a crucial oncogenic driver in TNBC and other aggressive solid tumors (glioblastoma, lung, pancreatic).
• FOXM1 overexpression, driven by TP53 mutations in TNBC, is a key factor in its aggressive phenotype.
• No FDA-approved FOXM1 inhibitors are currently available, and none have entered clinical trials.

Conclusions:

• FOXM1 is a validated therapeutic target for aggressive cancers, especially TNBC.
• Development of effective FOXM1 inhibitors is crucial for advancing cancer treatment strategies.
• Targeting FOXM1 represents a potential breakthrough for managing chemoresistant and metastatic cancers.