Autophagy dysfunctions associated with cancer cells and their therapeutic implications

Abstract

Genomic analysis of human cancers indicates that the loss or mutation of core autophagy related genes, (ATG) is uncommon, whereas oncogenic events that activate autophagy and lysosomal biogenesis have been identified. Several studies have demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles in cells: a cellular process that maintains the homeostasis of the normal cell, while self-defects can lead to a lawsuit to accelerate tumorigenesis and developing diseases, such as cancer. Depending on different contexts, autophagy dysfunctions may play a role: neutral, tumor-suppressive, or tumor-promoting.The process of autophagy may function in tumor suppression by mitigating metabolic stress and, in concert with apoptosis, by preventing tumor cell death by necrosis. In this case, optimal combination of autophagy inhibition (CQ, HCQ) with other conventional therapies - chemo or radiotherapy in a variety of tumor types in different phases can be successful approaches for improve the effect of anticancer therapies. This review examines recent insights of the molecular mechanism of autophagy and the potential roles of autophagy in cell death, cancer development, overview of the most recent therapeutic strategies involving autophagy modulators in cancer prevention and therapeutic opportunities.