Dietary modulation of CMA: implications for cancer prevention and therapy

Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that links nutrient availability to intracellular proteostasis through the targeted turnover of selective cytosolic proteins. Through this selective control of protein quality, CMA participates in the regulation of metabolic adaptation, cellular homeostasis, and stress responses. CMA is highly responsive to nutritional cues, including caloric restriction (CR), fasting, and changes in macronutrient composition, positioning this pathway as a key mediator of cellular adaptation to metabolic stress. In cancer, CMA displays context-dependent functions that influence tumor metabolism, genomic stability, and survival under adverse microenvironmental conditions. These dual roles suggest that dietary modulation of CMA may shape tumor initiation and progression through effects on cellular proteostasis and metabolic plasticity. In this review, we summarize current knowledge on the molecular mechanisms by which nutritional signals regulate CMA and discuss the physiological implications of nutrition-driven CMA modulation for cancer prevention and therapy.