Cancer Cell Metabolic Reprogramming: Dietary, Pharmacological Strategies and Clinical Perspectives

Metabolic reprogramming, a key feature of cancer progression that enables tumor adaptation to stress and therapy, represents an emerging target in anticancer research through dietary and pharmacological modulation. Dietary strategies such as caloric restriction (CR), intermittent fasting, and nutrient-specific modifications are emerging approaches to target oncogenic metabolism. Preclinical studies show that CR reduces tumor burden and inhibits IGF-1/mTOR signaling, while restoring immune pathways. Complementary preclinical evidence confirms that pharmacological inhibitors of the IGF-1R and mTOR pathways independently expose metabolic vulnerabilities, while concurrent autophagy blockade alongside mTOR inhibition can further reduce cancer cell viability by preventing stress adaptation. Multi-omics analyses facilitate the identification of how dietary restriction and pharmacological interventions remodel the tumor microenvironment by altering immune infiltration and stromal interactions, and uncover metabolic dependencies, that represent actionable therapeutic vulnerabilities. These findings suggest that dietary and pharmacological metabolic modulation represents an innovative approach in anticancer research. Preclinical models demonstrate the capability of these interventions to suppress tumor growth and enhance therapeutic responses, while early-phase clinical trials currently establish their safety and biological feasibility. In this review, we aim to summarize findings from in vitro models, in vivo animal studies, clinical observations, and multi-omics analyses to assess the potential of diet and pharmacological mimetics in influencing tumor metabolism and the tumor microenvironment.