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Updated: Nov 26, 2025

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
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Current and future landscape of poly (ADP-ribose) polymerase inhibition resistance

Emily Hinchcliff1, Anca Chelariu-Raicu2, Shannon N Westin1

  • 1Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Current Opinion in Obstetrics & Gynecology
|December 14, 2020
PubMed
Abstract

Insights

Strategies to overcome poly(ADP-ribose) polymerase (PARP) inhibitor resistance are crucial. Research is exploring combinations and DNA-damaging agents to enhance PARP inhibitor efficacy in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are effective in homologous recombination-deficient tumors.
  • PARPi resistance can emerge, limiting long-term treatment benefits.
  • Understanding PARPi resistance mechanisms is essential for improving cancer therapy.

Purpose of the Study:

  • To review strategies for overcoming PARP inhibitor resistance.
  • To present ongoing and completed clinical trials investigating these strategies.

Main Methods:

  • Review of clinical evidence and ongoing trials.
  • Analysis of resistance mechanisms including BRCA promoter demethylation and reversion mutations.

Main Results:

  • PARPi resistance can develop through specific genetic alterations.
  • Combinations of PARPi with antiangiogenic, PI3K/AKT/mTOR, or MEK inhibitors are under investigation.
  • Enhancing DNA damage with chemotherapy or cell cycle inhibitors is also being explored.

Conclusions:

  • There is a significant clinical need for strategies to enhance PARPi efficacy and overcome resistance.
  • Further research and clinical trials are necessary to establish optimal treatment paradigms for PARPi-resistant tumors.

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