Cancer cell glucose metabolism

Cancer cell glucose metabolism, frequently termed the Warburg effect, represents a fundamental metabolic reprogramming where malignant cells preferentially utilize aerobic glycolysis instead of oxidative phosphorylation, even in oxygen-rich environments (Warburg, O., Science, 1956). This shift facilitates the rapid generation of adenosine triphosphate (ATP) and provides essential metabolic intermediates for the biosynthesis of macromolecules like nucleic acids and lipids, which are critical for sustained cell proliferation and tumor growth (Vander Heiden et al., Science, 2009). Therapeutic strategies targeting this process focus on inhibiting key enzymatic nodes—such as Hexokinase 2 (HK2), Phosphofructokinase 1 (PFK1), and Lactate Dehydrogenase A (LDHA)—or blocking glucose transporters like GLUT1 (SLC2A1) to starve the tumor (Ganapathy-Kanniappan & Geschwind, Mol Cancer, 2013). Furthermore, the export of lactate via monocarboxylate transporters (MCTs) is targeted to induce intracellular acidification and disrupt the tumor microenvironment (Payen et al., Cancer Metastasis Rev, 2020). Despite its potential, the clinical application is challenged by the metabolic requirements of normal tissues, necessitating the identification of cancer-specific isoforms or therapeutic windows to avoid systemic toxicity (Hay, N., Nat Rev Cancer, 2016).

Other names

Warburg effectAerobic glycolysis in cancerMetabolic reprogrammingTumor glycolysis

Inhibition of rate-limiting glycolytic enzymes (e.g., HK2, PFK1, LDHA), competitive blockade of glucose uptake through GLUT transporters, and inhibition of lactate efflux via monocarboxylate transporters (MCTs).