Carglumic acid promotes apoptosis and suppresses cancer cell proliferation in vitro and in vivo.

Drug repurposing is a therapeutic strategy that applies drugs to treat different diseases based on new therapeutic function. Carglumic acid (Carbaglu; Orphan Europe) is an orphan drug approved by the FDA for hyperammonemia. Administration of carglumic acid for treatment of hyperammonemia has few side effects and has been used for 10 years to effectively treat hyperammonemia symptoms of both adult and pediatric patients. Here, we tested the potential of carglumic acid to be repurposed as an anticancer agent and showed that carglumic acid promotes apoptosis and inhibits cancer cell growth ina wide variety of human cancers, including pancreatic ductal adenocarcinoma, triple-negative breast cancer (TNBC), hepatoma, and lung cancer. Our data from in vivo models indicates that orally taking 10% of the carglumic acid dose currently used for the treatment of hyperammonemia ise ffective to suppress the growth of pancreatic ductal adenocarcinomaand TNBC. If given intravenously, only 5% of the carglumic acid doseis needed to be effective against TNBC. These findings suggest that carglumic acid may serve as a safe and effective therapeutic to treat both TNBC and pancreatic cancer.