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, 39 (12), 847-854

Cancer Metabolism: Fueling More Than Just Growth


Cancer Metabolism: Fueling More Than Just Growth

Namgyu Lee et al. Mol Cells.


The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

Keywords: cancer; immune evasion; metabolism; metabolites; tumor microenvironment.


Fig. 1
Fig. 1
Overview of metabolic mechanisms involved in adaptation to intratumoral metabolic stress, maintaining stemness and immune evasion. Metabolic reprogramming of cancer cells enhances fitness toward intratumoral metabolic stress and immune surveillance, and contributes to maintaining stemness. GLUT1/3, Glucose transporter 1/3; PKM2, M2 isoform of pyruvate kinase; SHMT2, Serine hydroxymethyltransferase; LDHA, Lactate dehydrogenase A; NHE1, Na+/H+-exchanger; MCT1/4, Monocarboxylate transporters; CA9, Carbonic anhydrase 9; IDH*, Gain-of-function mutation in isocitrate dehydrogenase1/2; FH*, Loss-of-function mutation in fumarate hydratase; SDH*, Loss-of-function mutation in succinate dehydrogenase; PHD, Prolyl hydroxylases; HIF1α, Hypoxia-inducible factor 1α; KDMs, Histone lysine demethylases; TET, Ten eleven translocation family of 5-methylcytosine (3mC) hydroxylases; IDO1, Indoleamine-2, 3-dioxygenase 1; TDO2, tryptophan-2, 3-dioxygenase 2; CD73, Ecto-5′-nucleotidases; CD39, Ectonucleoside triphosphate diphosphohydrolase 1.

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