Therapeutics: Sterol O-acyltransferase 1 (SOAT1; ACAT1); programmed cell death 1 (PD-1; PDCD1; CD279)

Mouse studies suggest SOAT1 inhibitors, alone or in combination with PD-1 inhibitors, could help treat cancer. In a mouse model of primary melanoma, SOAT1 knockout in CD8+ T cells decreased tumor growth and increased survival compared with normal SOAT1 expression. In a mouse model of metastatic melanoma, SOAT1 knockout in CD8+ T cells decreased tumor growth and increased survival. In a mouse model of lung cancer, the SOAT inhibitor avasimibe decreased the number of tumors and tumor growth and increased survival compared with vehicle. In the mouse model of primary melanoma, avasimibe plus an anti-PD-1-antibody decreased tumor growth and increased survival compared with either agent alone. Next steps include testing inhibition of SOAT1 in various cancers.

Millendo Therapeutics Inc. has ATR-101, a selective inhibitor of SOAT1, in Phase I testing to treat adenocarcinoma and adrenal insufficiency, and preclinical testing to treat Cushing's disease. ...