Exploiting DNA repair defects in high-grade serous ovarian carcinoma

Abstract

High-Grade Serous Ovarian Carcinoma (HGSOC) is the most common subtype of ovarian cancer, and is the leading cause of ovarian cancer death. This subtype is molecularly characterised by frequent loss of Homologous Recombination (HR) DNA repair, making it susceptible to Poly-ADP ribose polymerase (PARP) inhibitor treatment. Despite the efficacy of PARP inhibitors (PARPi) in treating HGSOC, disease recurrence is common. A poor understanding of PARPi toxicity and resistance mechanisms has limited improvements in overall survival of patients. This project utilised HGSOC Patient-Derived Xenograft (PDX) and in vitro models to determine underlying mechanisms of PARPi sensitivity and resistance. Ch..