Autophagy in gastrointestinal cancers: Therapeutic and biological perspectives

Gastrointestinal (GI) neoplasms are among the most common and lethal tumors around the world. In spite of the introduction of multiple conventional therapeutics for GI tumors, the treatment of these cancers is challenging. Moreover, they are able to mediate resistance to therapeutics. Therefore, the novel therapeutics should be developed for the treatment of GI tumors based on the underlying mechanisms. Autophagy is a programmed cell death mechanism dysregulated in human cancers and it is a potential therapeutic target. In the current review, a special focus is placed on the role of autophagy in GI neoplasms. The current studies have highlighted the fact that genomic and epigenetic factors can participate in the regulation of autophagy in GI tumors. Autophagy can exert protective function to enhance survival of cancer cells, while it decreases apoptosis, ferroptosis and other cell death mechanisms. On the other hand, the pro-death autophagy impairs the progression of GI tumors. In order to regulate autophagy in GI tumor therapy, the studies have focused on the development of drugs (synthetic drugs and natural compounds) along with nanoparticles for the autophagy modulation in GI cancer therapy. The autophagy-related factors can be considered as prognostic and diagnostic factors in GI tumors.