Cancer cell death by programmed necrosis?

A recent paper by Zong et al. [2004. Alkylating DNA damage stimulates a regulated form of necrotic cell death. Genes Dev. 18, 1272-12821 describes how alkylating agents kill cells by a process they term "programmed necrosis," induced by excessive activation of PARP resulting in degradation of cytosolic NAD(+) and inhibition of glycolysis. We argue that it is not obvious whether chemotherapy in patients can induce sufficient NAD(+) loss to affect glycolysis; that the "programmed" nature of the necrosis requires more evidence; and that there are mechanisms making cancer cells hypersensitive to DNA damage other than their high rate of aerobic glycolysis. (c) 2004 Elsevier Ltd. All rights reserved.