New Investigator Research Grant Program

Acute myeloid leukemia (AML) is an aggressive blood cancer, leading to the growth of abnormal white blood cells. While some patients are cured with current therapies and bone marrow transplants, most patients still see their cancer return, and fewer than one-third survive five years. As a result better and safer treatments are urgently needed. We have created a new drug called AOH1996 that inhibits caPCNA, a cancer-associated protein that leukemia cells rely on for their cell growth. AOH1996 disrupts the metabolism of leukemia cells, causing them to die while sparing normal bone marrow cells. In mice with AML, AOH1996 extended the survival from 35 days with no treatment to 50 days. When AOH1996 was combined with azacitidine and venetoclax, drugs used as conventional care treatment of unfit AML patients, survival stretched to roughly 160 days, about twice what azacitidine and venetoclax achieve on their own. Importantly, data from an ongoing human clinical trial of AOH1996 in solid tumors have not shown major side effects, suggesting this drug may improve treatment without adding additional toxicity. We are preparing a clinical trial of single-agent AOH1996 in patients whose AML has returned or resisted earlier therapies, and plan to test it in combination with existing treatments in the future.