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2018-10-19

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cc-by (c) Romeo, M. et al., 2018
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/215715

Translational research opportunities regarding homologous recombination in ovarian cancer

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https://doi.org/10.3390/ijms19103249

Abstract

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. Keywords: BRCA1; BRCA2; PARP inhibitors; deficient homologous recombination; high-grade serous ovarian cancer; mechanisms of resistance; ovarian cancer.

Subject

Assaigs clínics, Medicaments antineoplàstics, Càncer d'ovari

Subject (English)

Clinical trials, Antineoplastic agents, Ovarian cancer

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Articles publicats en revistes (Ciències Clíniques)

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ROMEO, Margarita, et al. Translational research opportunities regarding homologous recombination in ovarian cancer. International Journal of Molecular Sciences. 2018. Vol. 19, num. 10. ISSN 1661-6596. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/215715

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