Autophagy modulation in cancer
Summary
Autophagy is a highly conserved, finely regulated and lysosome-dependent biological process through which eukaryotic cells mobilize metabolites in response to nutrient deprivation and dispose of supernumerary or toxic cytoplasmic entities to ensure cellular quality control. In line with the notion that autophagy globally preserves cellular homeostasis, defects in the molecular machinery for autophagy generally favour malignant transformation. Conversely, proficient autophagic responses are
Content
# Autophagy modulation in cancer
*Published: 2026 May 18*
Autophagy is a highly conserved, finely regulated and lysosome-dependent
biological process through which eukaryotic cells mobilize metabolites in
response to nutrient deprivation and dispose of supernumerary or toxic
cytoplasmic entities to ensure cellular quality control. In line with the notion
that autophagy globally preserves cellular homeostasis, defects in the molecular
machinery for autophagy generally favour malignant transformation. Conversely,
proficient autophagic responses are often beneficial to developing tumours as
they support the survival of malignant cells facing harsh microenvironmental
conditions. Finally, the ability of neoplastic cells to undergo autophagy
influences their susceptibility to anticancer immune responses in a
context-dependent manner. Thus, although autophagy stands out as a major target
to intercept cancer at multiple inflection points of the disease,
one-size-fits-all approaches are inherently incapable of capturing the complex
influence of autophagy on the cancer cell (immuno)biology as a whole. Further
complicating this scenario, healthy cells, including tumour-targeting immune
effectors, rely on autophagy for their maturation, survival and functions, and
pharmacological autophagy inhibitors currently available for use in humans are
intrinsically nonspecific. Here, we discuss the promise and limitations of
targeting autophagy to limit malignant transformation, exacerbate cancer cell
death as driven by conventional therapeutics and restore immunosurveillance in
support of superior disease responses to immunotherapy.
DOI: 10.1038/s41573-026-01449-9