Context-dependent role of SIRT3 in cancer.

Sirtuin 3 (SIRT3), an NAD+ -dependent deacetylase, plays a key role in the modulation of metabolic reprogramming and regulation of cell death, as well as in shaping tumor phenotypes. Owing to its critical role in determining tumor-type specificity or the direction of tumor evolution, the development of small-molecule modulators of SIRT3, including inhibitors and activators, is of significant interest. In this review, we discuss recent studies on the oncogenic or tumor-suppressive functions of SIRT3, evaluate advances in SIRT3-targeted drug discovery, and present potential avenues for the design of small-molecule modulators of SIRT3 for cancer therapy.