We propose a model for synergistic killing of human cancer cells that relies on the combined increase in production of ceramide, likely through ABT-263-induced BAK activation, with inhibition of ceramide metabolism to its pro-proliferative metabolites glucosylceramide or sphingosine-1-phosphate, by either inhibition of glucosyceramide synthase (GCS) or inhibiton of sphingosine kinase (Fig. 7A), respectively. The gene discussed is BAK1; the disease is cancer.