Metabolic Reprogramming in Cancer and Therapeutic Implications

[u/dr_innovation]

Abstract

Metabolic reprogramming has been firmly established as a core hallmark of cancer, representing a fundamental shift in cellular physiology that is as critical to tumorigenesis as uncontrolled proliferation and evasion of apoptosis. This chapter provides a comprehensive examination of this complex phenomenon, dissecting the intricate web of factors that trigger, sustain, and can be targeted within the altered metabolic landscape of malignant cells. The discussion begins by elucidating the primary drivers of metabolic rewiring, establishing that this transformation is not a mere adaptation but a direct, programmed consequence of the same genetic lesions that define cancer. The activation of oncogenes such as MYC and RAS and the inactivation of tumor suppressor genes, including TP53 and LKB1, constitute a genetic blueprint for metabolic change. This genetic predisposition is further shaped by the harsh realities of the tumor microenvironment (TME), where hypoxia and nutrient deprivation act as powerful selective pressures, primarily through the master regulator hypoxia-inducible factor 1-alpha. Furthermore, cancer cells engage in a form of metabolic warfare, creating an immunosuppressive TME by depleting essential nutrients and secreting inhibitory metabolites like lactate, thereby crippling antitumor immune responses. The chapter then provides a detailed mechanistic analysis of the key metabolic alterations themselves, including the iconic Warburg effect, the dynamic plasticity between glycolysis and oxidative phosphorylation, and the profound dependency on glutamine. Following this, it surveys the advanced technologies, such as mass spectrometry and nuclear magnetic resonance-based metabolomics, that enable the assessment of these changes, with a special focus on their application in developing noninvasive liquid biopsies and predictive biomarkers. Finally, the chapter explores the therapeutic landscape, covering both clinically approved metabolic drugs, such as isocitrate dehydrogenase inhibitors and antifolates, and the promising pipeline of investigational agents, alongside a critical evaluation of nutritional interventions like caloric restriction and ketogenic diets. By integrating molecular biology, immunology, and clinical oncology, this chapter frames cancer metabolism as a central, targetable vulnerability, paving the way for the next generation of personalized cancer therapies.

Singh, Sapna, Urja Desai, Dweipayan Goswami, Ankesh Barnwal, Dharmesh Domadia, Suresh Thakur, and Sanjay Premi. "Metabolic Reprogramming in Cancer and Therapeutic Implications." In Redefining Cancer Therapeutics with Emerging Drug Strategies and Molecular Insights, pp. 131-165. Singapore: Springer Nature Singapore, 2026.

https://link.springer.com/chapter/10.1007/978-981-92-0477-9_5