Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair.

ABSTRACT:

Purpose

Emergence of mismatch repair (MMR) deficiency is a frequent mechanism of acquired resistance to the alkylating chemotherapeutic temozolomide (TMZ) in gliomas. Poly(ADP-ribose) polymerase inhibitors (PARPi) have been shown to potentiate TMZ cytotoxicity in several cancer types, including gliomas. We tested whether PARP inhibition could re-sensitize MSH6-null MMR-deficient gliomas to TMZ, and assessed the role of the base excision repair (BER) DNA damage repair pathway in PARPi-mediated effects.

Experimental design

Isogenic pairs of MSH6 wild-type and MSH6-inactivated human glioblastoma (GBM) cells (including both IDH1/2 wild-type and IDH1 mutant), as well as MSH6-null cells derived from a patient with recurrent GBM were treated with TMZ, the PARPi velipa

SUBMITTER: Higuchi F 

PROVIDER: S-EPMC7192178 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature