Necrosis, and then stress induced necrosis-like cell death, but not apoptosis, should be the preferred cell death mode for chemotherapy: clearance of a few misconceptions

Ju Zhang1, Xiaomin Lou1, Longyu Jin2, Rongjia Zhou3, Siqi Liu1, Ningzhi Xu4, and D. Joshua Liao2

1 CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, P.R. China

2 Hormel Institute, University of Minnesota, Austin, MN, USA

3 Department of Genetics & Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan, P. R. China

4 Laboratory of Cell and Molecular Biology, Cancer Institute, Academy of Medical Science, Beijing, P.R. China


D. Joshua Liao, email:

Keywords: Apoptosis, Cancer therapy, Carcinogenesis, Evolution, Hyperthermia

Received: June 19, 2014 Accepted: July 3, 2014 Published: July 4, 2014


Cell death overarches carcinogenesis and is a center of cancer researches, especially therapy studies. There have been many nomenclatures on cell death, but only three cell death modes are genuine, i.e. apoptosis, necrosis and stress-induced cell death (SICD). Like apoptosis, SICD is programmed. Like necrosis, SICD is a pathological event and may trigger regeneration and scar formation. Therefore, SICD has subtypes of stress-induced apoptosis-like cell death (SIaLCD) and stress-induced necrosis-like cell death (SInLCD). Whereas apoptosis removes redundant but healthy cells, SICD removes useful but ill or damaged cells. Many studies on cell death involve cancer tissues that resemble parasites in the host patients, which is a complicated system as it involves immune clearance of the alien cancer cells by the host. Cancer resembles an evolutionarily lower-level organism having a weaker apoptosis potential and poorer DNA repair mechanisms. Hence, targeting apoptosis for cancer therapy, i.e. killing via SIaLCD, will be less efficacious and more toxic. On the other hand, necrosis of cancer cells releases cellular debris and components to stimulate immune function, thus counteracting therapy-caused immune suppression and making necrosis better than SIaLCD for chemo drug development.

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