Enzyme-based autophagy in anti-neoplastic management: From molecular mechanisms to clinical therapeutics

Autophagy is an evolutionarily conserved self-cannibalization process commonly found in all eukaryotic cells. Through autophagy, long-lived or damaged organelles, superfluous proteins, and pathogens are sequestered and encapsulated into the double-membrane autophagosomes prior to fusion with lysosomes for ultimate degradation and recycling. Given that autophagy is deemed both protective and detrimental in malignancies, the clinical therapeutic utilization of autophagy modulators in cancer has attracted immense attentions over the past decades. Dependence of tumor cells on autophagy during amino acid insufficiency or deprivation has prompted us to explore the underlying autophagy regulatory mechanisms to inject amino acid degrading enzymes and enzyme-based strategies into therapeutic maneuvers of autophagy in cancer. •Autophagy is both protective and detrimental in malignancies.•Tumor cells are dependent on autophagy during amino acid deprivation.•Amino acid degrading enzymes may be targets for enzyme-based regulation of autophagy.