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Updated: Feb 5, 2026

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Androgen Receptor Inhibitor Enhances the Antitumor Effect of PARP Inhibitor in Breast Cancer Cells by Modulating DNA

Ahrum Min1,2, Hyemin Jang1, Seongyeong Kim1

  • 1Cancer Research Institute, Seoul National University, Seoul, Korea.

Molecular Cancer Therapeutics
|September 21, 2018
PubMed

Insights

A novel androgen receptor (AR) inhibitor, AZD3514, enhances breast cancer cell sensitivity to olaparib by downregulating DNA damage response (DDR) pathways. This combination therapy shows promise for treating AR-positive breast cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Androgen receptor (AR) is a therapeutic target in 60-70% of breast cancers.
  • Novel AR inhibitors are needed to treat AR-expressing breast cancers.

Purpose of the Study:

  • Investigate the efficacy of a novel AR inhibitor, AZD3514, in breast cancer.
  • Determine AZD3514's effect on DNA damage response (DDR) pathways.
  • Evaluate AZD3514 in combination with olaparib.

Main Methods:

  • Treatment of breast cancer cell lines with AZD3514 and olaparib.
  • Analysis of DNA damage response (DDR) molecule expression (ATM, chk2).
  • Assessment of NKX3.1 expression and degradation.
  • Xenograft model studies.

Main Results:

  • AZD3514 alone had minimal antiproliferative effect but downregulated DDR molecules (ATM, chk2).
  • AZD3514 enhanced sensitivity to olaparib by blocking DDR.
  • AZD3514 induced NKX3.1 degradation via TOPORS upregulation.
  • Combined AZD3514/olaparib showed antitumor effects by compromising DDR.

Conclusions:

  • AZD3514 combined with olaparib demonstrates a rationale for clinical trials in AR-positive and TOPORS-expressing breast cancers.
  • Targeting AR and DDR pathways offers a novel therapeutic strategy for breast cancer.

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