Translational research opportunities regarding homologous recombination in ovarian cancer
Romeo, Margarita (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pardo, Juan Carlos (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez Cardús, Anna (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez Balibrea, Eva (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Quiroga, Vanesa (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Martínez Román, Sergio (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Sole, F (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Margelí, Mireia (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Mesía, Ricard (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Date:	2018
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.
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article de revisió ; Article ; Versió publicada
Subject:	Ovarian Cancer ; High-grade serous Ovarian Cancer ; Deficient homologoys recombination ; PARP inhibitors ; BRCA1 ; BRCA2 ; Mechanisms of resistance
Published in:	International journal of molecular sciences, Vol. 19 Núm. 10 (19 2018) , p. 3249, ISSN 1422-0067

DOI: 10.3390/ijms19103249
PMID: 30347758

18 p, 288.5 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Published articles