Cancer Metabolism: Recent Advances in Biochemical Mechanisms and Targeted Therapeutic Strategies

Background: Cancer is characterized not only by genetic and epigenetic abnormalities but also by profound alterations in cellular metabolism. Metabolic reprogramming enables malignant cells to meet the increased requirements for energy production, biosynthesis, redox regulation, proliferation, invasion, and adaptation to the tumor microenvironment. Although aerobic glycolysis, commonly referred to as the Warburg effect, remains a central feature of cancer metabolism, contemporary research has demonstrated that tumor cells utilize highly flexible metabolic networks involving glucose, glutamine, lipids, amino acids, one-carbon metabolism, mitochondrial oxidative phosphorylation, and redox pathways. [1,2] Objective: To review recent advances in the biochemical mechanisms underlying cancer metabolic reprogramming and to summarize emerging therapeutic strategies targeting metabolically vulnerable pathways in malignant cells. Methods: A narrative literature review was undertaken over a period of 6–8 months at Mahavir Institute of Medical Sciences. Relevant literature addressing cancer metabolism, metabolic reprogramming, glycolysis, glutamine metabolism, lipid metabolism, mitochondrial metabolism, oncometabolites, tumor microenvironment, metabolic plasticity, and metabolism-targeted therapies was reviewed. PubMed-indexed literature and major biomedical publications were considered, with particular emphasis on recent reviews and mechanistic studies. The literature was synthesized thematically according to major metabolic pathways and therapeutic targets. Results: The reviewed literature indicates that cancer cells undergo coordinated metabolic remodeling involving increased glucose uptake and glycolysis, altered tricarboxylic acid cycle activity, enhanced glutamine utilization, increased nucleotide and lipid biosynthesis, altered amino-acid metabolism, and adaptation of mitochondrial oxidative metabolism. Oncogenic signaling involving MYC, PI3K/AKT/mTOR, HIF-1?, and related pathways contributes substantially to this metabolic phenotype. [3,4] Accumulation of oncometabolites such as 2-hydroxyglutarate, succinate, and fumarate can influence epigenetic regulation, cellular differentiation, hypoxia signaling, and tumor progression. [5,6] Therapeutic strategies targeting glycolysis, glutaminolysis, mutant IDH enzymes, fatty-acid synthesis, mitochondrial metabolism, one-carbon metabolism, and metabolic interactions within the tumor microenvironment are under active investigation. [7-12] However, metabolic plasticity, tumor heterogeneity, compensatory pathway activation, toxicity, and inadequate predictive biomarkers remain major barriers to clinical translation. Conclusion: Cancer metabolism represents a complex and adaptable network rather than a single metabolic abnormality. Advances in metabolomics, molecular profiling, and precision oncology are improving understanding of tumor-specific metabolic dependencies. Therapeutic targeting of metabolic vulnerabilities, particularly when combined with conventional anticancer treatment or immunotherapy, may provide new opportunities for individualized cancer treatment. Future clinical development will require reliable biomarkers to identify metabolically vulnerable tumors and rational combination strategies capable of overcoming metabolic adaptation. Keywords: cancer metabolism; metabolic reprogramming; Warburg effect; glycolysis; glutamine metabolism; lipid metabolism; oncometabolites; tumor microenvironment; targeted therapy; precision oncology