Brain Cancer Project

In the United States, more than 100,000 people, including over 20,000 children, have malignant brain cancer, and every year, 25,000 people are newly diagnosed with the disease. Glioblastoma accounts for 30% of malignant brain tumors and is the one that has the worst prognosis: only 3% of treated patients survive 5 years. Despite all efforts, no significant advancements have been made in the past 30 years and the diagnosis of glioblastoma remains a death sentence.

Treatment options for glioblastoma are limited. Surgery is the primary choice of treatment, but patient survival increases by only 6-12 months. This is because cancer stem cells that cannot be removed surgically regenerate into larger and more aggressive tumors. Therefore, post-surgical chemotherapy is critical. However, most chemotherapeutics fail to eradicate the tumor cells because they penetrate only poorly across the blood-brain barrier into the brain.

The main problem for successful drug delivery into the brain and tumor tissue is a group of transporters at the blood-brain and blood-tumor barriers. Recent studies indicate that two of these transporters, P-glycoprotein and BCRP, work together as a “gatekeeper team” and limit chemotherapeutics from entering the brain and reaching the tumor tissue.

To overcome this clinical obstacle, we focus on targeting a signaling mechanism to turn off both P-glycoprotein and BCRP and are currently testing this strategy. Our approach can potentially help increase brain uptake of chemotherapeutics, which is an important step towards improving chemotherapy of brain tumors in general and glioblastoma in particular.