Glioblastoma multiforme (GBM) is a disease of the entire brain. Both primary and metastatic brain tumors have limited treatment options and long term survival is rare. Even in the face of aggressive treatment, brain tumor growth and recurrence is unavoidable, due mainly to ineffective delivery of therapeutic agents across the blood-brain barrier (BBB). The BBB in the tumor core is "leaky", allowing systemic drug delivery, but glioma cells infiltrate normal brain structures centimeters away from the margin of surgical resection where the BBB is intact.
In this project, the enhanced expression and transport capacity of large neutral amino acid transporter (LAT1) both at the BBB and in glioma cells is utilized to develop novel and effective prodrugs of anti-cancer drug palbociclib with improved tumor targeting properties.