Treatment of brain tumors

Glioblastoma (GBM) is a uniformly fatal disease. The location and invasive nature of GBM renders complete surgical resection impossible. Although radiotherapy is important for disease management, side effects prohibit the delivery of curative doses. Despite the successful introduction of novel targeted therapeutics in some other solid cancer types, clinical trials in GBM have all failed. The mission of our preclinical research group is to develop and validate more effective pharmacotherapies for this disease. One of the spearheads of our research is aimed at highlighting the important role of the blood-brain barrier (BBB) in treatment failures. Although disruption of the BBB is common, this grossly affects areas of the tumor that can be surgically resected. However, the non-resectable tumor cells that have colonized the surrounding normal brain tissue are protected by the BBB and are the source of the inevitable recurrence. Just a few mainly small hydrophobic drugs display some efficacy against GBM. In particular, drug transporting proteins like ABCB1 (P-gp) and ABCG2 (BCRP) hinder the entry of most of the other effective anticancer agents, including many targeted agents. Thus, in order to develop more successful pharmacotherapy, our research aims to identify potentially useful agents that are no or weak substrates of these drug transporters. Alternatively, we are trying to improve drug penetration into brain tumors by using drug efflux pump inhibitors or carrier systems.

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