Title: Heterogeneous Drug Penetration into Human Brain Tumors: Mechanistic and Quantitative Insights from In Vitro, In Silico and Patients
Speaker: Jing Li, PhD, Associate Professor, Department of Oncology, Wayne State University School of Medicine; Director, Pharmacology Core, Karmanos Cancer Institute
Insufficient penetration of potentially effective chemotherapeutic agents across the human blood-brain barrier (BBB) is a huge hurdle to successful treatment of brain cancer. Mechanistic understanding and early, quantitative prediction of drug BBB penetration is of paramount importance to rational drug development and treatment for brain cancer. However, the penetration of many new and existing anticancer agents into human brain and brain tumors remains understudied, underreported, or misunderstood because of the difficulty to accessing human brain specimens and the lack of in vitro assays or animal models that can reliably predict human BBB permeability. This knowledge deficit is further compounded by the lack of translational research methodologies that bridge laboratory work and clinical study.
By collaboration between clinical pharmacologists and neurosurgical oncologists, we have developed an integrated translational research program that leverages in vitro drug metabolism and transport studies, pharmacokinetic modeling, and clinical trials to better understand and predict drug penetration across the intact and disrupted BBB in patients with brain cancer (particularly glioblastoma), in a mechanistic and quantitative manner. This presentation will discuss our approach and major findings in this area.