Conference Proceedings
Loss of RAD51C promoter hypermethylation confers PARP inhibitor resistance
Rachel M Hurley, Ksenija Nesic, Cordelia McGehee, Olga Kondrashova, Maria I Harrell, Paula A Schneider, Xiaonan Hou, Cristina Correia, Karen S Flatten, Giada V Zapparoli, Alexander Dobrovic, Kevin K Lin, Thomas C Harding, Andrea E Wahner Hendrickson, Elizabeth M Swisher, Matthew Wakefield, S John Weroha, Clare L Scott, Scott H Kaufmann
CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2018
Abstract
Abstract Background: Acquired PARP inhibitor (PARPi) resistance in high-grade serous ovarian cancer (HGSOC) as a result of restored homologous recombination has been observed following secondary mutations that restore full-length protein in BRCA1, BRCA2, RAD51C, and RAD51D. Additionally, loss of BRCA1 methylation has also been shown to confer resistance. However, little is known about the role of RAD51C methylation in acquired PARPi resistance. In ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib in ovarian carcinoma, four (2%) tumors demonstrated RAD51C methylation. The present study utilizes HGSOC patient derived xenografts (PDXs) and recurrent samples from ARIEL2 to ass..
View full abstract