Reconsidering Cancer Through a Systemic Metabolic Perspective: A Holistic Approach to Tumor Metabolism and Clinical Evidence

Abstract

Cancer has traditionally been viewed as a genetic disease driven by accumulated mutations; however, growing evidence indicates that metabolic dysregulation also plays an important role in tumor initiation and progression. This review aims to evaluate the evidence supporting a systemic metabolic perspective of cancer by integrating molecular, cellular, and clinical findings related to tumor metabolism. Key metabolic alterations such as aerobic glycolysis (Warburg effect), mitochondrial dysfunction, altered lipid and amino acid metabolism, and redox imbalance are critically examined in the context of cancer development. In addition, to clarify the bidirectional relationship between genetic and metabolic changes, the interaction between metabolic reprogramming and oncogenic signaling pathways, and clinical evidence supporting metabolic interventions such as metabolic inhibitors and retargeted drugs targeting tumor bioenergy are also discussed. The common conclusion drawn from all these parameters in light of the current findings is that explaining cancer metabolism solely as a consequence of genetic mutations is insufficient; current evidence suggests that metabolic alterations may actively contribute to tumor initiation and progression. Therefore, incorporating systemic metabolic perspectives may facilitate future advances in early diagnosis, therapeutic targeting, and personalized oncology.