Harnessing of Programmed Necrosis for Fighting against Cancers

Chemotherapy has long been considered as one of useful strategies for cancer treatment. It is primarily based on the apoptosis that can selectively kill cancer cells. However, cancer cells can progressively develop an acquired resistance to apoptotic cell death, rendering refractory to chemo- and radiotherapies. Although the mechanism by which cells attained resistance to drug remains to be clarified, it might be caused by either pumping out of them or interfering with apoptotic signal cascades in response to cancer drugs. In case that cancer cells are defective in some part of apoptotic machinery by repeated exposure to anticancer drugs, alternative cell death mechanistically distinct from apoptosis could be adopted to remove cancer cells refractory to apoptosis-inducing agents. This review will mainly deal with harnessing of necrotic cell death, specifically, programmed necrosis and practical uses. Here, we begin with various defects of apoptotic death machinery in cancer cells, and then provide new perspective on programmed necrosis as an alternative anticancer approach.