Temozolomide Resistance in Glioblastoma Multiforme: Mechanisms, Ramifications, and Potential Solutions to an Urgent Clinical Problem

Glioblastoma multiforme (GBM) is the most common and malignant type of brain cancer. Current standard therapy for GBM involves surgery followed by ionizing radiation treatment with temozolomide (TMZ), a DNA-alkylating agent. At molecular level, TMZ produces several distinct DNA lesions such as N7 -methylguanine, N3 -methyladenine, O6 -methylguanine that all produce cytostatic cytotoxic effects against cells. The unique nature each lesion requires cells utilize mutually exclusive repair pathways to effectively correct damage inflicted TMZ. face value, diversity in suggests drug resistance would be relatively rare occurrence after treatment. Unfortunately, this not case. While does extend post-operative survival months, patients develop anti-cancer agent which significantly reduces overall survival. This review assesses important clinical problem examining cellular mechanisms responsible activity well associated inherent TMZ-induced resistance.