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PARP inhibitor combination therapy

Amy Dréan1, Christopher J Lord1, Alan Ashworth2

  • 1The CRUK Gene Function Laboratory, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London SW3 6JB, UK.

Critical Reviews in Oncology/Hematology
|December 10, 2016
PubMed

Insights

Olaparib, the first Poly(ADP-ribose) polymerase (PARP) inhibitor, targets BRCA-mutated cancers. Combining PARP inhibitors with other therapies shows promise, with ongoing research into their clinical utility and future challenges.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Olaparib, the first Poly(ADP-ribose) polymerase (PARP) inhibitor, was approved in 2014 for cancer treatment.
  • PARP inhibitors exploit synthetic lethality to target tumors with BRCA1/BRCA2 mutations when used as single agents.
  • PARP inhibition demonstrates potential when combined with other therapeutic modalities.

Purpose of the Study:

  • To review preclinical and clinical evidence supporting the use of PARP inhibitor combinations.
  • To discuss the future prospects and challenges associated with combinatorial PARP inhibitor therapies.

Main Methods:

  • Literature review of preclinical studies on PARP inhibitor combinations.
  • Analysis of clinical trial data for PARP inhibitor combination therapies.
  • Discussion of emerging trends and obstacles in the field.

Main Results:

  • Preclinical data support the efficacy of various PARP inhibitor combinations.
  • Clinical evidence indicates promising outcomes for certain combination strategies.
  • Several challenges remain, including toxicity management and patient selection.

Conclusions:

  • PARP inhibitor combinations represent a promising therapeutic strategy in oncology.
  • Further research is needed to optimize combination regimens and overcome existing challenges.
  • Future directions include exploring novel combinations and predictive biomarkers.
Keywords:
BRCA1BRCA2Drug combinationsPARP inhibitor

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