118-LQP-JABS 20260903105711 Lumina Quest Publishing m.arslansohail@gmail.com Lumina Quest Publishing Journal of Advanced Biological Sciences J. Adv. Biol. Sci. 3134-8823 10.66590/jabs https://lquestpub.com/archives.php?journal=journal-of-advanced-biological-sciences 12 30 2025 12 30 2025 2 2 10.66590/jabs20250202 https://lquestpub.com/articles-list.php?journal=journal-of-advanced-biological-sciences&volume=2&issue=2 Ketogenic and Calorie-Restricted Diets in Cancer: Molecular Mechanisms, Metabolic Vulnerabilities and Translational Evidence Fahmida Khatoon Muhab Suliman Sumia Fadul Ahmed Ali Mukhtar Mahgoub Fatima Hamadain Alnourain Hamed R. Ahmed Sahoud Al-sultany Mohammed Abdelrazig Ahmed Elrofaie Fatima Diab Mohammed Osman Maha M. Abdul-Latif Cancer is characterized by dynamic metabolic reprogramming that enables malignant cells to sustain proliferation, biosynthesis, redox balance and adaptation to nutrient and treatment stress. This metabolic plasticity has prompted interest in Ketogenic Diets (KDs) and Calorie-Restricted (CR) interventions as potential adjuncts to anticancer therapy. KDs primarily alter carbohydrate availability, ketogenesis and systemic insulin signaling, whereas CR reduces total energy availability and engages cellular energy-sensing pathways. This review synthesizes the biological rationale, molecular mechanisms, preclinical findings and human clinical evidence linking these interventions with cancer metabolism. Particular attention is given to the insulin/IGF-1–PI3K/AKT/mTOR axis, AMP-activated protein kinase, mitochondrial metabolism, oxidative stress, autophagy, ketone-body signaling and tumor–microenvironment interactions. Available evidence indicates that dietary metabolic interventions can modify systemic glucose and other metabolic variables and may influence treatment response in selected experimental models. However, clinical evidence for improvements in tumor control or survival remains limited and heterogeneous. Importantly, metabolic plasticity differs among tumors and nutritional restriction may be harmful in patients with cachexia, sarcopenia, or inadequate intake. The current evidence therefore supports KDs and CR approaches as investigational, biomarker-informed adjuncts rather than replacements for established cancer treatment. Future trials should use standardized dietary protocols, objective measures of adherence and ketosis, metabolic and molecular biomarkers, body-composition assessment and clinically meaningful oncological outcomes. 12 30 2025 12 30 2025 22 29 10.66590/jabs2025020206 https://lquestpub.com/article/10.66590/jabs2025020206