BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression

Abstract

Cancer: a drug combination for combating melanoma Drugs that target proteins involved in issuing stop and start commands to cancer-related genes help to sensitize melanoma cells to a widely used anti-cancer therapy, leading to tumor shrinkage in mice. Furong Zeng from Central South University in Changsha, China, and colleagues screened 240 approved anti-cancer agents in search of molecules that work synergistically with a BET inhibitor, an inhibitor of these proteins, to induce the death of melanoma cells. They found that a protein targeted by BET inhibitors (JQ1 and NHWD-870) regulates a growth factor protein, whose altered expression then helps to sensitize melanoma cells to sunitinib. Sunitinib is approved to treat several types of cancer and works by targeting many different kinds of kinase enzymes. The combination of BET inhibitors and sunitinib showed synergistic antitumor effects in a mouse model of melanoma.