DEVELOPMENT OF HDAC11 INHIBITORS AND THEIR APPLICATION IN KRAS-DRIVEN CANCERS

Abstract

HDAC11 is the most recently discovered and the least studied HDAC. In recent years, it has been reported to have crucial roles in immune function, metabolism, and tumorigenesis. During my Ph.D., I have worked on developing selective HDAC11 inhibitors that do not impede other HDAC’s activity and exploring natural products as a potential HDAC11 inhibitor such as Garcinol. I then applied my developed inhibitors in different types of cancer cells. Surprisingly, HDAC11 inhibition potently suppressed the anchorage-independent growth of KRAS dependent pancreas and colon cancer cells. Our preliminary data suggest that HDAC11 inhibitors could be potential therapeutics for KRAS-driven cancers and may provide a possible solution for the long-term challenge of targeting KRAS.