Chapter 9 - Role of multidrug resistance in glioblastoma chemoresistance: Focus on ABC transporters

Abstract

Glioblastoma (GBM) is the most frequent and aggressive primary cancer of the brain in adults. Despite aggressive therapeutic interventions, the median overall survival is below 18 months after initial diagnosis. The current standard of care for patients with newly diagnosed GBM includes concurrent administration of temozolomide (TMZ) and radiotherapy followed by adjuvant TMZ. Since 2005, TMZ remained the first-line chemotherapy in the treatment of GBM patients with its ability to cross the blood–brain barrier. However, after initial efficacy, GBM cells acquire resistance to TMZ and other chemotherapeutic agents via multiple mechanisms, including the expression of ATP-binding cassette (ABC) efflux proteins. These transporters not only are involved in normal physiological functions, i.e., physiological cholesterol transport and elimination of toxins, but also play a role in pathological conditions, i.e., chemotherapies drug resistance. In humans, each ABC protein has specific tissue locations and specific functions. In this review, we highlight the role of ABC protein superfamily members ABCB1, ABCC1, and ABCG2 in the resistance of GBM cells to chemotherapy.