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PARP inhibitor resistant BRCA-mutated advanced breast cancer: current landscape and emerging treatments

Carmine Valenza1,2, Renato Maria Marsicano1,2, Dario Trapani1,2

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

Current Opinion in Oncology
|September 9, 2024
PubMed
Abstract

Insights

Patients with advanced breast cancer (aBC) resistant to PARP inhibitors (PARPi) face limited treatment options. Research is ongoing to understand resistance mechanisms and develop new therapies for this challenging condition.

Area of Science:

  • Oncology
  • Genetics
  • Pharmacology

Background:

  • Advanced breast cancer (aBC) patients treated with PARP inhibitors (PARPi) often develop treatment resistance.
  • Understanding the molecular mechanisms driving PARPi resistance is crucial for improving patient outcomes.

Purpose of the Study:

  • To review the treatment landscape for PARPi-resistant BRCA-mutated aBC.
  • To explore innovative therapies and the molecular basis of resistance.

Main Methods:

  • Literature review of studies on PARPi resistance in BRCA-mutated aBC.
  • Analysis of treatment options post-PARPi failure.
  • Classification of PARPi resistance mechanisms.

Main Results:

  • Antibody-drug conjugates and non-platinum-based chemotherapy (PBC) are current options post-PARPi failure.
  • On-target PARPi resistance mechanisms include reversions (60%) and non-reversions (40%).
  • Specific resistance alterations may reduce the efficacy of PARPi and PBC, requiring further clinical validation.

Conclusions:

  • PARPi-resistant aBC presents a significant unmet clinical need due to a lack of targeted therapies and biomarkers.
  • Further research is essential to elucidate resistance mechanisms and develop effective biomarker-driven treatment strategies.

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