Drug Discovery Research for Aggressive Cancers

Project 1: Targeting HIF-1 and TRAP1 in Human Glioblatoma Cancer

Glioblastoma (GBM) is the most lethal primary brain tumor diagnosed both in children and adults. The patient survival rate, even under current aggressive treatment strategies such as surgery, radiotherapy, and chemotherapy, is only 15 months.  Mechanistic investigation and new therapeutic approaches for glioblastoma treatment are urgently needed. Overexpression of TNF receptor-associated protein 1 (TRAP1) and Hypoxia-inducible factor-1 (HIF-1) play critical roles in GBM cell growth and invasion. In this project, we investigate these two key molecular pathways and their simultaneous inhibitions by small molecule inhibitors as a therapeutic approach for GBM cancers.

Project 2: Targeting HIF-1 and CD73 in Human Esophageal Cancer.

Esophageal cancer is one of the most aggressive cancers with a poor prognosis, and the overall 5-year survival rate is less than 20 percent. Mechanistic investigation and new therapeutic approaches for treatment improvements are urgently needed. Overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and immunosuppressive CD73, an ecto-5’-nucleotidase enzyme, contribute to tumor progression and drug resistance in cancer. We hypothesize that simultaneous targeting of CD73 and HIF-1α could be an important therapeutic approach for EAC. Therefore, in this proposal, we will 1) investigate the expressions of CD73 and HIF-1 in hypoxic cells of esophageal cancer and 2) identify a new CD73 inhibitor and investigate its combinatorial effect with HIF-1α inhibitor on EAC progression and invasion.