New anticancer agents are in great demand due to the heterogeneous nature of cancer and the development of resistance to existing drugs. This collaborative research with Robert Weiss, Biomedical Sciences, Richard Cerione, Molecular Medicine, and Hening Lin, Chemistry and Chemical Biology, aims to establish SIRT5 inhibition as new strategy to treat cancers.

SIRT5 is a key regulator of several metabolic proteins upon which cancer cells are dependent. Weiss, Cerione, and Lin are determining how blocking SIRT5 inhibits malignant transformation and tumorigenesis. They are working to understand the detailed molecular functions of SIRT5 in cancer cells, as well as in the tumor microenvironment.

The discoveries will shed light on the unique dependencies of cancers on metabolic alterations, knowledge that can help the development of novel therapeutics for treating cancer.

The researchers are also developing additional SIRT5 inhibitors with improved in vivo efficacies and testing them in mouse models of breast cancer. There is robust translational potential of the project, which is based on fundamental understanding of the enzymatic activity and biochemistry of SIRT5—coupled with biological analyses in cultured cells and mice.