Abstract
David Cheresh, PhD, is professor and vice chair of pathology at the University of California San Diego and serves as the director of translational research at the Moores Cancer Center. He is also associate director for the Institute of Engineering and Medicine. Dr. Cheresh’s research laboratory focuses on tumor and vascular biology and has uncovered new molecular mechanisms that regulate tumor growth and angiogenesis.
Dr. Cheresh’s research addresses the molecular basis of cancer but also focuses on translating his discoveries into practical therapeutic options for cancer patients. Some of his past research discoveries have led to the development of therapeutics to treat cancer and target both the tumor and tumor-associated vasculature. In particular, Dr. Cheresh discovered that integrin anb3, a cell adhesion receptor found highly expressed on invasive tumor cells and angiogenic endothelial cells, plays a crucial role in the growth and vascularization of tumors. This discovery and subsequent work in the Cheresh laboratory led to the development of two drugs now in late-stage clinical testing in cancer patients. One of these drugs, cilengitide, has shown promise in patients with glioblastoma. In phase II clinical trials, cilengitide has produced a significant survival benefit in patients with this deadly form of cancer. Cilengitide has recently completed Phase III clinical trials for patients with glioblastoma. If this trial is successful, cilengitide will be approved for brain tumor patients in the coming months. Current efforts ongoing in the Cheresh laboratory are aimed at understanding the molecular basis of cilengitide’s activity to better predict which cancer patients are most likely to respond to this drug.
Most recently, the Cheresh laboratory has focused on how microRNAs influence blood vessel growth in tumors and regulate the “angiogenic switch,” which enables tumors to access a blood supply. The laboratory has also described a new drug discovery platform that targets tumor- and vascular-associated kinases by chemically locking them in the inactive state. To this end, a new drug is being developed that allosterically inhibits RAF kinase and has shown strong inhibitory activity against breast cancer, pancreatic cancer, and brain cancer in preclinical models. One near-term goal of this research effort is to test this drug in patients with late-stage cancer at the Moores Cancer Center.