Inhibition of DNA Repair in Combination with Temozolomide or Dianhydrogalactiol Overcomes Temozolomide-Resistant Glioma Cells.

ABSTRACT: Resistance to temozolomide and intratumoral heterogeneity contribute to the poor prognosis of glioma. The mechanisms of temozolomide resistance can vary within a heterogeneous tumor. Temozolomide adds a methyl group to DNA. The primary cytotoxic lesion, O6-methylguanine, mispairs with thymine, leading to a futile DNA mismatch repair cycle, formation of double-strand breaks, and eventual cell death when O6-methylguanine DNA methyltransferase (MGMT) is absent. N7-methylguanine and N3-methyladenine are repaired by base excision repair (BER). The study aim was to elucidate temozolomide resistance mechanisms and identify methods to overcome temozolomide resistance in glioma. Several temozolomide-resistant clones were analyzed. Increased homologous recombination and mismatch repair system defici

SUBMITTER: Ohba S 

PROVIDER: S-EPMC8197190 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature