Book Chapter
The development of drug resistance through reversion mutation in BRCA genes in ovarian cancer
EL Christie, AE Freimund, S Fereday, K Alsop, T Hoang, K Pishas, G Au-Yeung, M Friedlander, DD Bowtell
Overcoming Ovarian Cancer Chemoresistance | Elsevier | Published : 2020
Abstract
BRCA1 and BRCA2 tumor suppressor genes are central components of the homologous recombination (HR) DNA repair pathway, a high-fidelity process required to maintain genome integrity in the presence of DNA damaging agents. Germline or somatic mutation in BRCA1 or BRCA2, and methylation of BRCA1 therefore strongly influence response of patients with high-grade serous ovarian cancer (HGSC) to chemotherapy or poly ADP ribose polymerase inhibitors (PARPi). The profound sensitivity of HR-defective HGSC to chemotherapy and PARPi provides a strong selective pressure for tumor cells that have partially or wholly restored HR repair function. Here we focus on mechanisms by which restoration of activity ..
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