Targeted Metabolic Therapy in Cancer: A Comprehensive Metabolic Treatment Strategy.

Cancer progression arises from the convergence of three domains: intrinsic metabolic and signaling rewiring within tumor cells, microenvironmental conditions that support survival and dissemination, and systemic metabolic dysfunction in the host. These layers collectively drive treatment resistance, immune evasion, and recurrence.  Targeted metabolic therapy (TMT) is proposed as a comprehensive therapeutic framework designed to simultaneously target all three domains of cancer progression. TMT targets key metabolic pathways implicated in tumor growth and survival such as glycolysis, glutaminolysis, IGF-1/PI3K-AKT-mTOR, angiogenesis, apoptosis resistance, and Wnt/β-catenin signaling, while also disrupting microenvironmental drivers including cancer stemness, metastasis, acidosis, hypoxia, and chronic inflammation. At the systemic (host) level, TMT corrects metabolic derangements - including hyperglycemia, systemic inflammation, and cachexia - that create a permissive environment for tumor progression. The therapeutic model integrates multiple intervention categories. These include dietary and fasting strategies, repurposed pharmacological agents, nutraceuticals, and essential vitamins and minerals. Additional components encompass oxygen- and redox-modulating therapies and lifestyle optimization measures. This paper outlines the biological rationale for TMT and proposes a systems-level framework for applying coordinated metabolic pressure with the aim of improving treatment responsiveness, prolonging survival, and offering cancer patients a more durable path toward disease control and remission.