Examining the Role of Specialized DNA Polymerases in the Development of Temozolomide Resistance in Glioblastoma Multiforme

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 can extend post-operative survival, most patients develop resistance to which leads significant increase in mortality. At molecular level, produces variety different DNA lesions including N7-methylguanine, N3-methyladenine, O6-methylguanine. Although each lesion possesses unique structure, they all elicit cytostatic cytotoxic effects against GBM cells. This review article describes cellular mechanisms accounting for anti-cancer activity as well responsible both inherent TMZ-induced drug resistance. Special emphasis placed on understanding roles various polymerases play toward initiation progression addition mediating TMZ. concludes discussions several new approaches show promise combating TMZ-resistance, specifically using small molecules block replication catalyzed polymerases.