IN THE SPOTLIGHT Not Expecting the Unexpected: Diacylglycerol Kinase Alpha as a Cancer Target

Summary: In this issue of Cancer Discovery, Dominguez and colleagues identify diacylglycerol kinase alpha (DGKα), an enzyme that converts the membrane lipid diacylglycerol to phosphatidic acid, as a central node upstream of mTOR and other oncogenic pathways. Importantly, targeting DGKα causes apoptosis in cancer cells and tumor growth inhibition in mice with no overt toxicity, implicating DGKα as a novel cancer-specifi c target. Cancer Discov; 3(7); 726–7. ©2013 AACR. See related article by Dominguez et al., p. 782 (8). In addition to surgery and radiation, chemotherapy is a widely used treatment modality for patients with cancer. On the basis of the observation that soldiers who were exposed to spilled sulfur mustards had depleted bone marrow and lymph nodes, the use of nitrogen mustard as a chemothera-peutic agent has its origins in the 1940s ( 1). The past seven decades since have seen an unprecedented explosion of our understanding of the disease, leading to the identifi cation of numerous cancer chemotherapeutics ( 1). With biologic an