Cancer Metabolic Reprogramming: From the Warburg Effect to Metabolic-Immune Regulation—Mechanistic Insights and Novel Targeted Therapeutic Strategies

Abstract

Cancer metabolism has been a benchmark of cancer cells. It has emerged as a critical area of cancer research decades ago, as it reprograms the traditional cellular metabolic cycles that facilitate cancer cells with rapid proliferation and resistance under stressful TME and immune surveillance. This review synthesizes the current understanding of these metabolic alterations, foundational metabolic mechanisms, especially including key signaling pathways and epigenetic modifications. With the Warburg effect as the foundation, the role of metabolites, such as lactate, in shaping the tumor microenvironment to promote immune evasion and tumor progression will be elucidated. Crucial signaling pathways and transcriptional regulators are also explored as pivotal contributors to metabolic reprogramming. Ultimately, this review critically discusses the latest innovative therapeutic strategies targeting cancer metabolism, based on these understandings, and highlights the promising metabolic modulators, especially metformin, for future clinical interventions. By connecting fundamental metabolic biology with emerging precision oncology strategies, particularly metabolism-based combination therapies, this paper outlines potential avenues for improving cancer patient outcomes and advancing personalized therapeutic approaches.