The treatment of both primary and secondary brain tumors is a serious unmet medical need in the field of neuro-oncology. Despite advances in developing molecularly-targeted anti-cancer therapeutics in treating peripheral tumors, there is no effective therapeutic for brain tumors that demonstrated dramatic improvement in patient survival. One of the major reasons of having lack of efficacy in central nervous system may be related to the delivery of therapeutic agents across the blood-brain barrier (BBB). The BBB expresses various transporters as well as unique junctional proteins that selectively permeate molecules into the brain from systemic circulation. Many molecularly-targeted therapeutic agents are found to be substrates of these efflux transporters at the BBB including P-glycoprotein (P-gp) and Breast cancer resistance protein (Bcrp). The current dissertation examined the multiple challenges in the treatment of brain tumors including non-specific protein binding, brain distributional kinetics, and role of efflux transporters on the distribution of various molecules such as molecularly-targeted anti-cancer drugs and tumor imaging agents.
University of Minnesota Ph.D. dissertation. November 2018. Major: Pharmaceutics. Advisor: William Elmquist. 1 computer file (PDF); xx, 272 pages.
Delivery and efficacy of targeted therapeutics and imaging agents for brain tumors.
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