Use of PARP inhibitors in breast and ovary cancer cell lines harboring mutations in genes of the homologous recombination DNA repair pathway

Abstract

It is known that breast and ovarian tumors with germline mutations in BRCA1 or BRCA2 genes are up to 1000 times more sensitive to treatment with PARP inhibitors than wild type tumors. Although, little is known about the effect of these PARP inhibitors on tumors harboring mutations in other genes involved in the homologous recombination mechanism of DNA repair. The objective of this work is to analyze if the protein expression presence/absence of genes involved in the homologous recombination mechanism of DNA repair is able to predict the response of tumors treated with PARP inhibitors. To this end, four cell lines from breast and ovarian cancer will be genetically edited using the CRISPR/Cas9 technology, eliminating several genes (one at each time) of the homologous recombination DNA repair pathway. In vitro experiments will be performed. In addition, bioinformatics analyses will be done with TCGA data. We believe that this work will clarify if patients harboring mutations in at least one of the homologous recombination DNA repair genes may benefit with the use of the targeted therapy of PARP inhibitors. (AU)