Assistant Professor Brigham and Women's Hospital, Harvard Medical School Boston, Massachusetts
Advanced brain cancers, including glioblastoma, are often incurable and have a high mortality rate. Even with aggressive treatment, the survival rate of patients has only improved slightly, from 11 months (with no treatment) to 14.6 months from the time of diagnosis. It is impossible to completely remove aggressive brain cancer cells by surgery because these cells invade into the surrounding normal brain tissue and cannot be easily identified. Cancer drugs administered via the bloodstream is often unable to reach these cells, as they are protected by a highly evolved and restrictive barrier called the blood-brain barrier, which separates brain tissue from circulating blood. Our mission is to address these dire clinical challenges by developing new targeted therapies that can effectively cross the blood-brain barrier and selectively seek out and destroy brain tumor cells. Conventional chemotherapy drugs travel throughout the body and can also damage normal healthy cells, causing severe side effects in patients. Improving our ability to direct these drugs specifically to the tumor should enable us to increase treatment effectiveness whilst reducing the unwanted side effects of chemotherapy. Here, we describe the development of a unique molecule that can cross the blood-brain barrier, as well as identify and home in on brain cancer cells. This allows us to target the tumor cell population with minimal harm to healthy tissues. This tumor-homing smart “missile” is called BTP-7. Our target is a deglycosylated isoform of the brevican protein, that is present only on the surface of brain cancer cells; and is not found in healthy tissue. BTP-7 binds to this protein and then becomes internalized by the brain tumor cells. Our plan is to chemically fuse a chemotherapeutic drug onto BTP-7 – like attaching a warhead onto a missile. We will generate many different BTP-7 missiles containing various types of anti-cancer drug to enable us to selectively attack and destroy the tumor. Findings from our research could help us develop the next generation of therapeutics to extend the lives of patients with advanced brain cancer, as well as improve the quality of life of the patients and their families. Ultimately, we aim to advance precision medicine in neuro-oncology.
Learning Objectives:
Understand therapeutic targeting to brain tumors
Define challenges and roadblock in drug delivery across the blood brain barrier