Glucose and Lactate, Starters or Intermediates of Cancer Metabolic Rewiring

Cancer cells undergo extensive metabolic reprogramming to sustain rapid proliferation and adapt to the hostile conditions of the tumor microenvironment. Central to this metabolic shift are glucose and lactate, which serve not only as essential energy substrates but also as potent signaling molecules that influence tumor growth, survival, and progression. This chapter explores the molecular mechanisms underlying enhanced glucose uptake and glycolytic metabolism in cancer cells, with a focus on their roles in supporting anabolic biosynthesis, promoting immune evasion, and activating key oncogenic signaling pathways, including HIF-1α, c-Myc, and the PI3K/Akt/mTOR axis. Furthermore, it delves into the evolving perception of lactate, not as a mere metabolic waste product, but as a dynamic fuel source, a modulator of tumor microenvironmental heterogeneity, and a driver of therapeutic resistance. By unraveling the complex interplay between glucose and lactate metabolism, this chapter provides deeper insight into the metabolic architecture of cancer and presents emerging strategies to target these vulnerabilities for more effective and personalized cancer therapies.