FOXM1: a potential therapeutic target in human solid cancers

ABSTRACT

Introduction: FOXM1 is one of the most frequently overexpressed proteins in human solid cancers. Here, we discuss novel direct targets of FOXM1 as well as new pathways involving FOXM1, through which this protein exerts its oncogenic activity.

Areas covered: We give a detailed review of FOXM1 transcriptional targets involved in 16 different types of human cancer as published in the literature in the last 5 years. We also discuss a novel positive feedback loop between FOXM1 and AKT – both well-established master regulators of cancer.

Expert opinion: Despite the discovery of several FOXM1 inhibitors over the years (by our team and others), their therapeutic use is limited by their adverse off-target effects.

Newly-discovered proteins regulated by FOXM1 present a promising alternative approach to target its pro-cancer activity. In addition, targeting regulating proteins that take part in the positive feedback loop between FOXM1/AKT has the double advantage of suppressing both, and can lead to developing novel anti-cancer drugs.

KEYWORDS:

• AKT
• cancer
• FOXM1
• FOXM1/AKT loop
• transcription

Article highlights

• FOXM1 is involved in all hallmarks of human cancers, and overexpression of FOXM1 is associated with aggressiveness and poor survival rates in several solid tumors.

• FOXM1 exerts its pro-cancer activity through numerous downstream targets. Identifying the FOXM1 targets and their specific role in distinct types of human cancer is crucial in cancer management.

• FOXM1 is part of a number of cellular signaling pathways including the FOXM1/AKT positive feedback loop, which plays a pivotal role in the development and progression of many human malignancies.

• Therapeutic targeting of FOXM1, downstream targets of FOXM1, and signaling pathways involving FOXM1 provide novel strategies to develop potent anticancer agents.

This box summarizes the key points contained in the article.

Acknowledgments

We would like to thank Dr. Mikhail Chesnokov (University of Illinois) for editing the manuscript and mindful and valuable comments.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

The authors did not receive any specific funding for this work.