A CERTain Role for Ceramide in Taxane-Induced Cell Death
Drug Resistance, Neoplasm
An unexpected benefit of functional genomic screens is that at times they answer questions that they were not designed to ask. A siRNA screen reported by Swanton et al. in this issue of Cancer Cell reveals that silencing of spindle assembly checkpoint genes facilitates mitotic slippage, resulting in escape from taxane-induced cell death, aneuploidy, and chromosomal instability, hallmarks of taxane resistance. Unexpectedly, the screen disclosed that the sphingolipid ceramide is a key regulator of the taxane-mediated spindle assembly checkpoint and taxane-induced cell death. Ceramide metabolism thus serves as a legitimate target for modulation of taxane effect on tumors.