Warburg metabolism
Cancer cells burn glucose into lactate even with oxygen around: inefficient but fast, and it supplies building blocks. This is why an FDG PET scan lights up tumours.
Diagram
Pick a product above a diagram to see the nodes it hits and the escape routes below the block. Hover or tap any node or arrow for what it is; every node opens its target, glossary entry or the pathway page. Violet boxes are druggable targets.
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.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 5, Feeding the tumour: A tumour is a construction site that never stops.
Cancer cells burn glucose into lactate even with oxygen around: inefficient but fast, and it supplies building blocks. This is why an FDG PET scan lights up tumours.
Cancer metabolism. 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.
The molecular players
The proteins and genes at this stage, with their role and how many products act on each. Listed players come from the atlas; drawn players sit as nodes in the diagrams above.
A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
Where medicines act
Products grouped by the node they hit, most advanced first, with the cancers an approved product is linked to. Pick one above the diagram to see it light up.
- IvosidenibApprovedAcute myeloid leukaemiaBiliary tract cancer (cholangiocarcinoma)IDH1- and IDH2-mutated acute myeloid leukaemia
- VorasidenibApprovedGlioma & glioblastomaAstrocytoma, IDH-mutant (grades 2 to 4)Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
- EnasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemiaSinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
- OlutasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemia
- Oncomine Dx Target TestApprovedNon-small-cell lung cancerBiliary tract cancer (cholangiocarcinoma)
- HMPL-306Phase 3
- SafusidenibPhase 3
- TQB3454Phase 3
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
Open questions
What is not known at this stage: the atlas's own questions, the bottlenecks it bears on, and the ideas in the corpus that try to answer them.
- Do diet interventions (ketogenic, fasting-mimicking) change outcomes in randomised trials?
- Why has metabolic plasticity defeated almost every single-target metabolic drug?
- early clinicalresearchA phase 0 fund to test academic compounds in humans with microdoses and imaging
Before investing in a full trial, give a few patients a tiny dose of a new compound and use scans and blood tests to see whether it reaches the tumour and hits its target. Fund these small studies as a matter of routine.
- early clinicalresearchGroup trials by broken mechanism, not by organ or single mutation
Rare cancers often share a broken cellular machine even when they arise in different organs. Grouping patients by that shared fault makes trials possible.
- early clinicalphilanthropyOne definitive ketogenic diet trial in glioblastoma, then stop
Patients with brain tumours are sold ketogenic diets on the strength of mouse data and small feasibility studies. A single adequately powered trial with dietitian support would either prove it or let clinicians say clearly that it does not work.
- preclinical evidenceresearchDe-acidify the tumour so T cells can work in it
Tumours are acidic, and immune cells stop working in acid. Neutralising that acid, or blocking the pumps that create it, might let immunotherapy work.
- preclinical evidenceMap metabolic dependencies in the patient, not the dish
Metabolic drugs keep failing because tumours switch fuels. Measuring what a patient's tumour actually eats, with tracers and PET, could pick the right metabolic drug for the right tumour.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2023rctINDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade gliomaNew England Journal of Medicinechanged practice
- 2022reviewThe hallmarks of cancer metabolism: Still emergingCell metabolism
- 2017translationalRecurrent IDH2 R172X mutations in sinonasal undifferentiated carcinomaModern Pathologychanged practice
src/data/mechanics-atlas.ts). Players, medicines, escape routes, tests, ideas and papers are resolved from the knowledge graph at build time through the stage's pathways, targets and terms, so every item here has its own page and sources. Where a section is missing, the corpus has no record tied to the stage yet. Nothing here is medical advice; see about and methodology. Stage 5.1 of 56.