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Updated: Sep 3, 2025

Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma
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Portal Vein Injection of Colorectal Cancer Organoids to Study the Liver Metastasis Stroma

Published on: September 3, 2021

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FOXM1-CD44 Signaling Is Critical for the Acquisition of Regorafenib Resistance in Human Liver Cancer Cells

Kenly Wuputra1,2,3, Pi-Jung Hsiao4, Wen-Tsan Chang5,6,7

  • 1Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.

International Journal of Molecular Sciences
|July 27, 2022
PubMed

Insights

Regorafenib resistance in liver cancer is linked to forkhead box protein M1 (FOXM1) and cancer stem cells (CSCs). Targeting FOXM1-CD44 signaling may improve regorafenib treatment efficacy in hepatocellular carcinoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Regorafenib, a multikinase inhibitor, was FDA-approved in 2017.
  • Cancer stem cells (CSCs) contribute to therapeutic resistance.
  • Forkhead box protein M1 (FOXM1) regulates CSC stemness and chemotherapy resistance.

Purpose of the Study:

  • To investigate the relationship between FOXM1 and regorafenib resistance in liver cancer.
  • To explore the potential of targeting FOXM1-CD44 signaling to overcome regorafenib resistance.

Main Methods:

  • Generation of regorafenib-resistant HepG2 cell clones.
  • Analysis of FOXM1 and CSC marker expression in resistant cells and patient samples.
  • Correlation analysis between FOXM1 expression, regorafenib resistance, and patient survival.

Main Results:

  • Regorafenib-resistant HepG2 clones overexpressed FOXM1 and CSC markers.
  • Upregulation of FOXM1 and regorafenib resistance were observed in hepatocellular carcinoma patients.
  • Elevated FOXM1 expression correlated with poor survival rates in these patients.

Conclusions:

  • FOXM1 is closely associated with regorafenib resistance and survival in hepatocellular carcinoma.
  • Antagonizing FOXM1-CD44 signaling presents a potential strategy to enhance regorafenib's therapeutic efficacy.
Keywords:
CD44FOXM1cancer stem cell lineshepatocellular carcinomaregorafenib

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