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Updated: May 29, 2025

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

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Bemcentinib enhances sensitivity to estrogen receptor inhibitors in breast cancer cells

Gyeongmi Kim1, Se Hee Ahn2, Se-Kyeong Jang3

  • 1Division of Fusion Radiology Research, Korea Institute of Radiological and Medical Sciences, Seoul 01812, Republic of Korea; Department of Biotechnology, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea.

The International Journal of Biochemistry & Cell Biology
|February 3, 2025
PubMed

Insights

Bemcentinib, an AXL inhibitor, shows promise in overcoming tamoxifen resistance in estrogen receptor-positive breast cancer. This combination therapy synergistically induces cell death, even in resistant cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Estrogen receptor (ER)-positive breast cancer is common and treated with ER inhibitors like tamoxifen and fulvestrant.
  • Therapeutic resistance to ER inhibitors is a major clinical obstacle in breast cancer treatment.
  • Novel strategies are needed to improve treatment efficacy and overcome resistance.

Purpose of the Study:

  • To evaluate bemcentinib's potential to sensitize ER-positive breast cancer cells to ER inhibitors.
  • To investigate the underlying mechanisms of bemcentinib's action, including effects on S6K1 and STAT3 signaling.
  • To assess bemcentinib's efficacy in overcoming tamoxifen resistance.

Main Methods:

  • Utilized MCF7 breast cancer cells and tamoxifen-resistant MCF7-TR cells.
  • Administered bemcentinib (AXL inhibitor) alone and in combination with 4-hydroxytamoxifen (4-OHT) and fulvestrant.
  • Assessed cell death, S6K1 phosphorylation, and STAT3 activation.
  • Performed AXL knockdown experiments.

Main Results:

  • Bemcentinib decreased S6K1 phosphorylation and synergized with ER inhibitors to induce cell death.
  • Bemcentinib activated STAT3; STAT3 inhibition enhanced cell death with bemcentinib and 4-OHT.
  • The combination of bemcentinib and 4-OHT induced cell death in tamoxifen-resistant MCF7-TR cells.
  • AXL knockdown did not affect sensitivity to 4-OHT or S6K1 signaling, suggesting AXL-independent effects.

Conclusions:

  • Bemcentinib shows potential as a sensitizer to ER inhibitors in ER-positive breast cancer.
  • Combination therapy with bemcentinib may overcome tamoxifen resistance.
  • The sensitizing effects of bemcentinib appear to be independent of AXL expression, possibly mediated through S6K1 inhibition.
Keywords:
BemcentinibEstrogen receptor-positive breast cancerS6K1STAT3Tamoxifen resistance

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