Cell Death Mechanisms in Human Cancers: Molecular Pathways, Therapy Resistance and Therapeutic Perspective

Abstract

A prominent cause of death among patients is cancer that can result from somatic mutations and exposure to environmental factors, among others. The treatment of cancer has been possible through the application of chemotherapy and radiotherapy that mainly mediate cell death and DNA damage. However, the tumor cells are able to induce the alternative molecular pathways to enhance their survival and mediate resistance to conventional therapeutics. The dysregulation of cell death pathways can significantly improve the therapy resistance in tumors and enhance their progression. Therefore, present review has been dedicated into understanding the abnormalities in cell death pathways. The induction of apoptosis through intrinsic and extrinsic pathways has been of importance in cancer therapy and the apoptosis inhibition through Bcl-2 and XIAP upregulation can mediate drug resistance. Moreover, autophagy has shown tumor-promoting and tumor-suppressing roles in cancer. Both inhibition and induction of autophagy can change tumorigenesis. Necroptosis is another cell death that has some similarities with apoptosis such as involvement of caspase-8 in its regulation. Ferroptosis is an iron-dependent cell death that reduces tumorigenesis and can be also regulated autophagy. The induction of immunogenic cell death and pyroptosis in the tumor cells can affect the immune system for cancer therapy. In addition to phytochemicals and small molecules introduced for the regulation of cell death mechanisms in cancer, the nanoparticles have been also applied to facilitate cell death in tumor treatment.