Delineating the role of autophagy in driving the resistance to cancer chemotherapy

Abstract

The development of resistance is one of the major complications faced by an oncologist for cancer treatment. Autophagy plays a crucial role in driving this resistance against most antineoplastic therapies. The evolutionarily conserved autophagy process meant for quality control of cellular organelles and protein complexes is overwhelmed by proliferative signals from various carcinogens. This leads to the accumulation of defective oncogenic proteins leading to carcinogenesis. As the tumor proliferates and grows in size, it reboots its autophagy pathways to supplement its ever-growing need for nutrients, oxygen, and energy supply. This review will discuss various molecular mechanisms of how physiological and metabolic stressors modulate autophagy, which drives the cancer cell's journey from dormancy to survival by fuelling the metabolic pathways involving internal cell restructuring and reshaping the tumor microenvironment. Considering the preclinical success of autophagy modulators for cancer treatment, this review will bring a new perspective and mechanistic explanation for using autophagy inhibitors for curtailing tumor progression and later using autophagy inducers for preventing cancer remission. This review will also help to formulate or repurpose safer and effective stand-alone and combination anticancer treatment strategies involving autophagy modulators.

Keywords

• autophagy
• cancer
• chemotherapy
• treatment