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Small-molecule inhibitors targeting FOXM1: Current challenges and future perspectives in cancer treatments

Sanjeev Raghuwanshi1, Andrei L Gartel1

  • 1University of Illinois at Chicago, Department of Medicine, Chicago, IL 60612, USA.

Biochimica Et Biophysica Acta. Reviews on Cancer
|November 1, 2023
PubMed

Insights

Forkhead box protein M1 (FOXM1) drives cancer growth and resistance to chemotherapy. Inhibiting FOXM1 with small molecules shows promise as a novel therapeutic strategy for difficult-to-treat cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Forkhead box protein M1 (FOXM1) is a transcription factor crucial for cell proliferation.
  • FOXM1 is overexpressed in most human cancers, correlating with poor prognosis and cancer hallmarks.
  • FOXM1 dysregulation contributes to cancer cell migration, invasion, angiogenesis, and metastasis.

Purpose of the Study:

  • To review the clinical utility of FOXM1 as a therapeutic target.
  • To summarize and categorize small-molecule inhibitors targeting FOXM1 based on their mechanisms.
  • To discuss challenges and future directions for FOXM1 inhibition in cancer therapy.

Main Methods:

  • Literature review of studies on FOXM1 function in cancer.
  • Analysis of small-molecule inhibitors targeting FOXM1.
  • Categorization of inhibitors by their targeting mechanisms.
  • Discussion of clinical development stages and challenges.

Main Results:

  • FOXM1 overexpression is linked to cancer progression and chemoresistance.
  • Suppression of FOXM1 can enhance cancer cell sensitivity to anti-cancer drugs.
  • Several small-molecule inhibitors targeting FOXM1 are in various stages of development.

Conclusions:

  • Targeting FOXM1 with small-molecule inhibitors, especially in combination with existing drugs, offers a potential strategy for overcoming chemoresistance.
  • Further research and development are needed to address challenges and advance FOXM1 inhibitors into clinical practice.
  • FOXM1 remains a significant target for novel cancer therapeutics.
Keywords:
CancerCombination therapiesDrug resistanceFOXM1Inhibitors

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