Targeting mitochondrial metabolism as cancer therapy
Despite recent therapeutic advances, melanoma remains by far the most lethal skin cancer. In 2014, there were an estimated 76,100 new melanoma cases and 9,710 melanoma-related deaths in the US. A tremendous unmet need still exists for improved therapies to treat clinically advanced melanoma. In melanoma, as in many other cancer types, metabolism is rewired to meet the anabolic demands of uncontrolled cellular proliferation. Reversal of this metabolic reprogramming in melanoma induces regression of melanoma tumors in mice. However, no therapeutic strategies have been deployed clinically to take advantage of this vulnerability of melanoma. We have found that the SIRT5 deacylase, a member of the sirtuin protein family, is required for melanoma survival, through effects on metabolism. By contrast, normal cells and mice tolerate loss of SIRT5 without major ill effects. We seek to identify and optimize SIRT5 inibitors to test in cell- and mouse based melanoma models.
$900,000 grant from the Melanoma Research Alliance