TY  - JOUR
AU  - Berdis, Anthony
PY  - 2021
DA  - 2021/05/18
TI  - Examining the Role of Specialized DNA Polymerases in the Development of Temozolomide Resistance in Glioblastoma Multiforme
JO  - OBM Neurobiology
SP  - 096
VL  - 05
IS  - 02
AB  - Glioblastoma multiforme (GBM) is an extremely malignant type of primary brain tumor that exhibits a high mortality rate. Current standard therapy involves surgery followed by radiation and treatment with the DNA-alkylating agent, temozolomide (TMZ). While TMZ treatment can extend post-operative survival, most patients develop resistance to TMZ which leads to a significant increase in mortality. At the molecular level, TMZ produces a variety of different DNA lesions including N7-methylguanine, N3-methyladenine, and O6-methylguanine. Although each DNA lesion possesses a unique molecular structure, they all elicit cytostatic and cytotoxic effects against GBM cells. This review article describes the molecular and cellular mechanisms accounting for the anti-cancer activity of TMZ as well as the mechanisms responsible for both inherent and TMZ-induced drug resistance. Special emphasis is placed on understanding the roles that various DNA polymerases play toward the initiation and progression of GBM in addition to mediating resistance to TMZ. This review concludes with discussions on several new approaches that show promise in combating TMZ-resistance, specifically using small molecules to block the replication of DNA lesions catalyzed by various DNA polymerases.
SN  - 2573-4407
UR  - https://doi.org/10.21926/obm.neurobiol.2102096
DO  - 10.21926/obm.neurobiol.2102096
ID  - Berdis2021
ER  -