Journal article
Characterization of a RAD51C-silenced high-grade serous ovarian cancer model during development of PARP inhibitor resistance
RM Hurley, CD McGehee, K Nesic, C Correia, TM Weiskittel, RL Kelly, A Venkatachalam, X Hou, NM Pathoulas, XW Meng, O Kondrashova, MR Radke, PA Schneider, KS Flatten, KL Peterson, MA Becker, EM Wong, MS Southey, A Dobrovic, KK Lin Show all
Nar Cancer | OXFORD UNIV PRESS | Published : 2021
Abstract
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 nirapa..
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Awarded by National Institutes of Health
Awarded by Stand Up to Cancer
Funding Acknowledgements
National Institutes of Health [P50 CA136393, F30 CA213737, T32 GM072474, T32 GM085641]; Ovarian Cancer Research Alliance (to E.M.S., P.H., S.H.K.); Stand Up to Cancer [SU2C-AACR-DT16-15] (to A.E.W.H., E.M.S., S.J.W., S.H.K.); Stafford Fox Medical Research Foundation (to C.L.S., O.K., M.W., K.N.); National Breast Cancer Foundation of Australia (to A.D.); Mayo Foundation for Education and Research (to R.M.H., C.D.M., T.M., R.L.K., A.V.)