The Implications of Several Forms of Programmed Necrosis for Cancer Therapy

Abstract

The dogma that apoptosis and autophagy are the sole forms of Programmed Cell Death (PCD) is no longer accepted, due to the recent discovery of programmed necrosis, a non-apoptotic, non-autophagic form of PCD. Necroptosis, parthanatos, pyroptosis, and ferroptosis are all forms of programmed necrosis, as these types of cell death dismantle the cell in an ordered fashion that is distinctly different from apoptosis or autophagy. Several key cellular mediators and events in these types of PCD have been discovered. Here, we discuss the basic characteristics, molecular pathways, and possible implications of these lesser-known types of PCD in cancer treatment modalities such as chemotherapy and radiotherapy. Because resistance to apoptosis is often responsible for cancer treatment failures, novel therapeutic strategies that can activate alternative cell death programs have great appeal. Understanding the underlying mechanisms of these types of PCD may facilitate the development of diverse therapeutic strategies, particularly against apoptosis-resistant cancers.