Translational research opportunities regarding homologous recombination in ovarian cancer

Margarita Romeo, Juan Carlos Pardo, Anna Martínez-Cardús, Eva Martínez-Balibrea, Vanesa Quiroga, Sergio Martínez-Román, Francesc Solé, Mireia Margelí, Ricard Mesía

Research output: Contribution to journalReview articleResearchpeer-review

3 Citations (Scopus)

Abstract

© 2018 by the authors. Licensee MDPI, Basel, Switzerland. Homologous recombination (HR) is a DNA repair pathway that is deficient in 50% of high-grade serous ovarian carcinomas (HGSOC). Deficient HR (DHR) constitutes a therapeutic opportunity for these patients, thanks to poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi; olaparib, niraparib, and rucaparib are already commercialized). Although initially, PARPi were developed for patients with BRCA1/2 mutations, robust clinical data have shown their benefit in a broader population without DHR. This breakthrough in daily practice has raised several questions that necessitate further research: How can populations that will most benefit from PARPi be selected? At which stage of Ovarian Cancer should PARPi be used? Which strategies are reasonable to overcome PARPi resistance? In this paper, we present a summary of the literature and discuss the present clinical research involving PARPi (after reviewing ClinicalTrials.gov) from a translational perspective. Research into the functional biomarkers of DHR and clinical trials testing PARPi benefits as first-line setting or rechallenge are currently ongoing. Additionally, in the clinical setting, only secondary restoring mutations of BRCA1/2 have been identified as events inducing resistance to PARPi. The clinical frequency of this and other mechanisms that have been described in preclinics is unknown. It is of great importance to study mechanisms of resistance to PARPi to guide the clinical development of drug combinations.
Original languageEnglish
Article number3249
JournalInternational Journal of Molecular Sciences
Volume19
Issue number10
DOIs
Publication statusPublished - 19 Oct 2018

Keywords

  • BRCA1
  • BRCA2
  • Deficient homologous recombination
  • High-grade serous ovarian cancer
  • Mechanisms of resistance
  • Ovarian cancer
  • PARP inhibitors

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