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PARP inhibitors: Clinical utility and possibilities of overcoming resistance

Benjamin G Bitler1, Zachary L Watson1, Lindsay J Wheeler2

  • 1Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Colorado, Aurora, CO, United States.

Gynecologic Oncology
|October 18, 2017
PubMed

Insights

Poly (ADP-ribose) polymerase (PARP) inhibitors are effective treatments for ovarian cancer with homologous recombination deficiencies. This review explores their use, resistance, and management strategies for recurrent ovarian cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • PARP inhibitors represent a significant advancement in ovarian cancer treatment.
  • Homologous recombination (HR) DNA repair pathway deficiencies, including BRCA1/2 mutations, are present in nearly half of ovarian cancers.
  • Limited options exist for recurrent ovarian cancer, driving the development of novel therapies targeting DNA repair defects.

Purpose of the Study:

  • To review the clinical applications, toxicities, and resistance mechanisms of PARP inhibitors in ovarian cancer.
  • To explore novel biomarkers for predicting PARP inhibitor response.
  • To discuss strategies for managing PARP inhibitor-resistant ovarian cancer.

Main Methods:

  • Review of existing literature on PARP inhibitors in ovarian cancer.
  • Analysis of clinical trial data and FDA-approved indications.
  • Examination of mechanisms of resistance and potential therapeutic strategies.

Main Results:

  • PARP inhibitors are approved for recurrent ovarian cancer with HR deficiencies and show benefit in patients without HR deficiencies.
  • Three PARP inhibitors are FDA-approved, with two more in late-stage trials.
  • Acquired resistance to PARP inhibitors is a significant clinical challenge.

Conclusions:

  • PARP inhibitors have transformed ovarian cancer care, particularly for HR-deficient tumors.
  • Understanding and overcoming resistance are crucial for optimizing long-term patient outcomes.
  • Further research into biomarkers and combination therapies is needed to manage resistant disease effectively.
Keywords:
BRCA1/2 mutationOvarian cancerPARP inhibitorsTherapy resistance

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