Novel Drug for Hepatocellular Carcinoma

Type of Award: accelerator
Award Number: A-005
Award Period: September 2018 - August 2019
Amount Awarded: $ 100,000.00
PI(s): Richard Silverman, NU;

Abstract: Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths in men (6th in women) worldwide; yet, it is highly chemotherapy- and radiation therapy-resistant. The three approved drugs show little efficacy; consequently, prognosis for recovery is poor. My collaborator found that the gene for ornithine aminotransferase (OAT) is overexpressed in HCC. Using our OAT inhibitors, he showed for the first time that they significantly suppressed alpha- fetoprotein (AFP) secretion, a biomarker for HCC, in Hep3B cells and significantly suppressed AFP serum levels and tumor growth in patient-derived HCC-harboring mice, even at 0.1 mg/kg. The best compound has excellent mouse pharmacokinetics with 42% oral bioavailability; a 7-day repeat toxicology study found no adverse effects at 10 mg/kg. Overexpression of the OAT gene in HCC, and the ability to block the growth of HCC by OAT inhibitors, strongly support OAT as a potential new therapeutic target to inhibit HCC growth.