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The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

Mehran Makvandi1, Estifanos D Tilahun1, Brian P Lieberman1

  • 1University of Pennsylvania, Perelman School of Medicine, Department of Radiology and Division of Nuclear Medicine and Clinical Molecular Imaging, Philadelphia, PA 19104, USA.

Biochemical and Biophysical Research Communications
|October 11, 2015
PubMed
Abstract

Insights

Targeting the sigma-2 receptor with a novel compound effectively treated triple-negative breast cancer (TNBC) cell lines. This approach shows promise as a new therapeutic strategy for TNBC, a cancer lacking targeted treatments.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Triple-negative breast cancer (TNBC) presents significant challenges due to high relapse rates and mortality.
  • Unlike other breast cancer subtypes, TNBC lacks approved targeted therapies.
  • The sigma-2 receptor is overexpressed in TNBC and serves as a proliferation marker.

Purpose of the Study:

  • To evaluate the sigma-2 receptor as a therapeutic target for drug delivery in TNBC.
  • To assess the potential of sigma-2 receptor-targeting compounds as biomarkers for TNBC.

Main Methods:

  • Assessed pharmacological properties of sigma-2 compounds using competitive inhibition assays.
  • Measured sigma-2 receptor expression via radioligand receptor saturation studies.
  • Compared drug sensitivity of Taxol versus a sigma-2 targeted cytotoxic payload (SW IV-134) in three TNBC cell lines (MDA-MB-231, HCC1937, HCC1806).

Main Results:

  • The compound SW IV-134 demonstrated potent efficacy across all three TNBC cell lines tested.
  • MDA-MB-231 cells exhibited significantly higher sigma-2 receptor expression and greater sensitivity to SW IV-134.
  • SW IV-134 treatment led to measurable caspase 3/7 activation, indicating induced cell death.

Conclusions:

  • Targeting the sigma-2 receptor with a cytotoxic payload proved effective in TNBC cell lines.
  • This study provides proof-of-concept for developing a novel therapeutic platform for TNBC.
  • Further research is warranted to advance this targeted approach for patient care.
Keywords:
Drug deliverySigma-2Targeted therapyTriple-negative breast cancer

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