Cancers, Vol. 11, Pages 354: Exploring the Frequency of Homologous Recombination DNA Repair Dysfunction in Multiple Cancer Types
Cancers, Vol. 11, Pages 354: Exploring the Frequency of Homologous Recombination DNA Repair Dysfunction in Multiple Cancer Types
Cancers doi: 10.3390/cancers11030354
Authors:
Lucy Gentles
Bojidar Goranov
Elizabeth Matheson
Ashleigh Herriott
Angelika Kaufmann
Sally Hall
Asima Mukhopadhyay
Yvette Drew
Nicola J. Curtin
Rachel L O’Donnell
Dysfunctional homologous recombination DNA repair (HRR), frequently due to BRCA mutations, is a determinant of sensitivity to platinum chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi). In cultures of ovarian cancer cells, we have previously shown that HRR function, based upon RAD51 foci quantification, correlated with growth inhibition ex vivo induced by rucaparib (a PARPi) and 12-month survival following platinum chemotherapy. The aim of this study was to determine the feasibility of measuring HRR dysfunction (HRD) in other tumours, in order to estimate the frequency and hence wider potential of PARPi. A total of 24 cultures were established from ascites sampled from 27 patients with colorectal, upper gastrointestinal, pancreatic, hepatobiliary, breast, mesothelioma, and non-epithelial ovarian cancers; 8 were HRD. Cell growth following continuous exposure to 10 μM of rucaparib was lower in HRD cultures compared to HRR-competent (HRC) cultures. Overall survival in the 10 patients who received platinum-based therapy was marginally higher in the 3 with HRD ascites (median overall survival of 17...
Source: Cancers - Category: Cancer & Oncology Authors: Lucy Gentles Bojidar Goranov Elizabeth Matheson Ashleigh Herriott Angelika Kaufmann Sally Hall Asima Mukhopadhyay Yvette Drew Nicola J. Curtin Rachel L O ’Donnell Tags: Article Source Type: research
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