{"entity":{"id":"cancer-metabolism","kind":"pathway","name":"Cancer metabolism","aka":[],"tldr":"Cancer cells rewire how they eat. They burn glucose inefficiently but fast (the Warburg effect), gorge on glutamine and fats, and build the nucleotides and lipids needed to divide. This is why the FDG PET scan works, and why metabolism is a drug target.","summary":"Oncogenic signalling (PI3K/AKT/mTOR, MYC, HIF) drives aerobic glycolysis and lactate export, glutaminolysis for TCA anaplerosis, de novo lipogenesis (FASN, SCD), and one-carbon metabolism (SHMT, MTHFD2) for nucleotides and methylation. Mutant IDH1/2 produce the oncometabolite 2-HG. Metabolic plasticity lets tumours switch fuels, which is why single-target metabolic drugs (glutaminase inhibitor telaglenastat, negative in RCC) disappoint. Approved metabolic drugs are antimetabolite chemotherapies and IDH inhibitors; arginine deprivation (ADI-PEG20) is in phase 3 in mesothelioma. Diet interventions (fasting-mimicking, ketogenic) are in trials as adjuncts.","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Warburg_effect_(oncology)","links":[{"label":"Pavlova, Zhu & Thompson, The hallmarks of cancer metabolism (Cell Metabolism 2022)","url":"https://doi.org/10.1016/j.cmet.2022.01.007"}],"tags":["mechanism"],"related":[],"cancers":[],"sections":[],"technologies":["fdg-pet","cytotoxic-chemotherapy"],"targets":["idh","pik3ca","hif2a"],"drugs":["ivosidenib","vorasidenib"],"companies":[],"institutions":["mskcc","md-anderson","penn-abramson","francis-crick"],"pathways":["pi3k-akt-mtor","myc","hif-vhl"],"terms":["warburg-effect","deregulating-cellular-energetics","suv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-pavlova-cell-metab-2022"],"journals":[],"dependsOn":[],"notes":["Leading programmes: Thompson (MSK) and Vander Heiden (MIT/Koch) on metabolic dependencies; DeBerardinis (UTSW) on in vivo metabolism; Rabinowitz (Princeton/Ludwig) on nutrient flux."],"analogy":"A factory that switches from a clean, efficient power plant to burning everything it can find, fast and dirty, because speed matters more than efficiency when you are building a new factory every day.","nodes":[{"id":"glc","label":"Glucose (GLUT1)","x":10,"y":25},{"id":"glyc","label":"Aerobic glycolysis (Warburg)","x":30,"y":25},{"id":"lac","label":"Lactate export (MCT4)","x":50,"y":10},{"id":"tca","label":"TCA cycle","x":50,"y":50},{"id":"gln","label":"Glutamine → glutaminase","x":10,"y":65},{"id":"lipid","label":"De novo lipogenesis (FASN)","x":75,"y":30},{"id":"onec","label":"One-carbon (SHMT2, MTHFD2) → nucleotides","x":75,"y":70},{"id":"idh","label":"Mutant IDH → 2-HG","x":30,"y":85,"targetId":"idh"},{"id":"sig","label":"PI3K/AKT/mTOR, MYC, HIF","x":92,"y":50}],"edges":[{"from":"glc","to":"glyc","type":"activates"},{"from":"glyc","to":"lac","type":"activates"},{"from":"glyc","to":"tca","type":"activates"},{"from":"gln","to":"tca","type":"activates"},{"from":"tca","to":"lipid","type":"activates"},{"from":"glyc","to":"onec","type":"activates"},{"from":"tca","to":"idh","type":"activates"},{"from":"sig","to":"glyc","type":"activates"},{"from":"sig","to":"lipid","type":"activates"},{"from":"sig","to":"onec","type":"activates"}],"interventions":["Antimetabolite chemotherapy (5-FU, gemcitabine, methotrexate) exploits nucleotide demand","IDH inhibitors (ivosidenib, vorasidenib) block 2-HG","Glutaminase, MCT1, FASN, and arginine-deprivation agents in trials","FDG PET images the Warburg effect","Diet and metformin trials as adjuncts"]},"route":"/pathways/cancer-metabolism/","neighbours":{"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"}],"target":[{"id":"hif1a","kind":"target","name":"HIF-1α (HIF1A)","route":"/targets/hif1a/"},{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"},{"id":"idh","kind":"target","name":"IDH1 / IDH2","route":"/targets/idh/"},{"id":"myc-gene","kind":"target","name":"MYC","route":"/targets/myc-gene/"},{"id":"pik3ca","kind":"target","name":"PIK3CA / PI3K-alpha","route":"/targets/pik3ca/"}],"drug":[{"id":"ivosidenib","kind":"drug","name":"Ivosidenib","route":"/drugs/ivosidenib/"},{"id":"vorasidenib","kind":"drug","name":"Vorasidenib","route":"/drugs/vorasidenib/"}],"institution":[{"id":"penn-abramson","kind":"institution","name":"Abramson Cancer Center, University of Pennsylvania","route":"/institutions/penn-abramson/"},{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"},{"id":"mskcc","kind":"institution","name":"Memorial Sloan Kettering Cancer Center","route":"/institutions/mskcc/"},{"id":"francis-crick","kind":"institution","name":"The Francis Crick Institute","route":"/institutions/francis-crick/"}],"pathway":[{"id":"autophagy","kind":"pathway","name":"Autophagy","route":"/pathways/autophagy/"},{"id":"cachexia-biology","kind":"pathway","name":"Cancer cachexia","route":"/pathways/cachexia-biology/"},{"id":"choline-metabolism-in-cancer","kind":"pathway","name":"Choline metabolism in cancer","route":"/pathways/choline-metabolism-in-cancer/"},{"id":"ferroptosis-cell-death","kind":"pathway","name":"Ferroptosis & regulated cell death","route":"/pathways/ferroptosis-cell-death/"},{"id":"glutamine-metabolism","kind":"pathway","name":"Glutamine addiction","route":"/pathways/glutamine-metabolism/"},{"id":"keap1-nrf2","kind":"pathway","name":"KEAP1-NRF2 antioxidant pathway","route":"/pathways/keap1-nrf2/"},{"id":"lipid-metabolism-cancer","kind":"pathway","name":"Lipid synthesis, uptake & cholesterol","route":"/pathways/lipid-metabolism-cancer/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"nutrient-competition-tme","kind":"pathway","name":"Nutrient competition & metabolic immunosuppression","route":"/pathways/nutrient-competition-tme/"},{"id":"pi3k-akt-mtor","kind":"pathway","name":"PI3K / AKT / mTOR","route":"/pathways/pi3k-akt-mtor/"},{"id":"theories-of-cancer","kind":"pathway","name":"Theories of cancer: how the ideas connect","route":"/pathways/theories-of-cancer/"},{"id":"hif-vhl","kind":"pathway","name":"VHL / HIF oxygen sensing","route":"/pathways/hif-vhl/"}],"term":[{"id":"atavistic-theory-of-cancer","kind":"term","name":"Atavistic theory: cancer as a reversion to an ancient programme","route":"/terms/atavistic-theory-of-cancer/"},{"id":"deregulating-cellular-energetics","kind":"term","name":"Hallmark: reprogramming cellular metabolism","route":"/terms/deregulating-cellular-energetics/"},{"id":"hallmarks-synthesis","kind":"term","name":"Hallmarks of cancer as a synthesis of the theories","route":"/terms/hallmarks-synthesis/"},{"id":"metabolic-theory-of-cancer","kind":"term","name":"Metabolic theory of cancer: from Warburg to oncometabolites","route":"/terms/metabolic-theory-of-cancer/"},{"id":"suv","kind":"term","name":"Standardised uptake value (SUV)","route":"/terms/suv/"},{"id":"warburg-effect","kind":"term","name":"Warburg effect","route":"/terms/warburg-effect/"}],"paper":[{"id":"paper-pavlova-cell-metab-2022","kind":"paper","name":"The hallmarks of cancer metabolism: Still emerging","route":"/key-papers/paper-pavlova-cell-metab-2022/"}],"idea":[{"id":"idea-metabolic-vulnerability-mapping","kind":"idea","name":"Map metabolic dependencies in the patient, not the dish","route":"/ideas/idea-metabolic-vulnerability-mapping/"}],"cancer":[{"id":"pheochromocytoma-paraganglioma","kind":"cancer","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/cancers/pheochromocytoma-paraganglioma/"}]}}