Journal article

Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance.

Rachel M Hurley, Cordelia D McGehee, Ksenija Nesic, Cristina Correia, Taylor M Weiskittel, Rebecca L Kelly, Annapoorna Venkatachalam, Xiaonan Hou, Nicholas M Pathoulas, X Wei Meng, Olga Kondrashova, Marc R Radke, Paula A Schneider, Karen S Flatten, Kevin L Peterson, Marc A Becker, Ee Ming Wong, Melissa S Southey, Alexander Dobrovic, Kevin K Lin Show all

NAR Cancer | Oxford University Press (OUP) | Published : 2021


Acquired PARP inhibitor (PARPi) resistance in BRCA1- or BRCA2-mutant ovarian cancer often results from secondary mutations that restore expression of functional protein. RAD51C is a less commonly studied ovarian cancer susceptibility gene whose promoter is sometimes methylated, leading to homologous recombination (HR) deficiency and PARPi sensitivity. For this study, the PARPi-sensitive patient-derived ovarian cancer xenograft PH039, which lacks HR gene mutations but harbors RAD51C promoter methylation, was selected for PARPi resistance by cyclical niraparib treatment in vivo. PH039 acquired PARPi resistance by the third treatment cycle and grew through subsequent treatment with either nirap..

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