Metabolic axis of autophagy: A key player in tumor maintenance and opportunities for therapeutic exploitation

Core Tip

Core Tip: Autophagy is an evolutionary conserved catabolic process that ensures cell adaptability under stress conditions and maintains cellular homeostasis. Dysregulation of autophagy supports tumor growth where its paradoxical role (protective and supportive) appears to depend on tumor stage, driver mutations, tissue type and metabolic sensitivity. Production of metabolic fuel sources and extracellular energy in an autophagy dependent manner contribute to autophagic switch. Pharmacological inhibition of autophagy or depletion of core autophagic genes have been significantly shown to impair metabolism and suppress tumor proliferation. Many recent studies argue that disruption of autophagy/core autophagic genes may potentiate the genomic instability under metabolic stress conditions and drive tumor development. Paradoxical change in the functions of autophagy-dependent metabolic crosstalk in tumor maintenance and disease aggressiveness emphasizes the therapeutic exploitation of supplemental approaches.