FOXM1: a potential therapeutic target in human solid cancers

Expert Opin Ther Targets. 2020 Mar;24(3):205-217. doi: 10.1080/14728222.2020.1727888. Epub 2020 Feb 19.

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; FOXM1; FOXM1/AKT loop; cancer; transcription.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Drug Development
  • Forkhead Box Protein M1 / genetics*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Molecular Targeted Therapy*
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Proto-Oncogene Proteins c-akt / metabolism

Substances

  • Antineoplastic Agents
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Proto-Oncogene Proteins c-akt