FOCUS on SIRT6. Sirtuin 6 (SIRT6) is an NAD-dependent histone deacetylase shown to function as a tumor suppressor in several cancer types. However, the therapeutic potential of SIRT6 activation has not yet been explored (until now). In a paper just out in Cell Death and Disease, a group at Ben Gurion University of the Negev showed that the allosteric SIRT6 activator MDL-800 inhibited the proliferation and migration of squamous cell carcinoma cell lines in vitro and delayed tumor growth in xenograft models. Mechanistically, MDL-800 inhibited mTOR signaling which induced a compensatory feedback loop, limiting its anti-tumor activity. However, combined treatment with a PI3Kinase inhibitor disrupted this feedback loop and resulted in a synergistic anti-proliferative effect.
