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Targeting androgen receptors in patients with metastatic breast cancer

Lorenzo Guidi1,2,3, Dario Trapani1,2, Giuseppe Curigliano1,2

  • 1Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS.

Current Opinion in Oncology
|October 1, 2025
PubMed
Abstract

Insights

Antiandrogen therapies show limited efficacy in metastatic breast cancer, despite targeting androgen receptor (AR)-positive tumors. Future strategies involve combination therapies and novel agents to overcome resistance and improve outcomes.

Area of Science:

  • Oncology
  • Endocrinology
  • Pharmacology

Background:

  • Metastatic breast cancer (MBC) includes hormone receptor-positive and triple-negative subtypes.
  • Androgen receptor (AR) expression is increasingly recognized as a therapeutic target in specific MBC subtypes.
  • Current treatment paradigms for AR-positive MBC are evolving.

Purpose of the Study:

  • To review current clinical evidence on antiandrogen therapies for AR-positive MBC.
  • To explore future perspectives, including novel agents and combination strategies.
  • To discuss mechanisms of resistance and biomarker development for AR-targeted therapies.

Main Methods:

  • Systematic review of clinical trials and preclinical studies.
  • Analysis of data from AR-targeted agents in hormone receptor-positive and triple-negative MBC.
  • Evaluation of combination therapies and next-generation AR inhibitors.

Main Results:

  • Antiandrogen therapies demonstrate modest activity in AR-positive MBC, with variable efficacy.
  • Combination therapies (e.g., with CDK4/6 or PI3K/AKT/mTOR inhibitors) show promise in overcoming resistance.
  • New-generation agents (PROTACs, non-LBD inhibitors, epigenetic modulators) offer novel AR-targeting approaches.

Conclusions:

  • Clinical efficacy of current antiandrogen therapies in MBC remains limited, necessitating improved patient selection.
  • Validated predictive biomarkers are crucial for optimizing patient selection and treatment response.
  • Combination regimens and next-generation agents are key to overcoming resistance and improving outcomes in AR-driven breast cancers.
Keywords:
androgen receptorantiandrogen therapymetastatic breast cancer

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