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.
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.
In one picture
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.
Diagram
top- 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
Notes
top- Leading programmes: Thompson (MSK) and Vander Heiden (MIT/Koch) on metabolic dependencies; DeBerardinis (UTSW) on in vivo metabolism; Rabinowitz (Princeton/Ludwig) on nutrient flux.
Pages like this
not linked directly; found by shared links- PathwaymRNA translation (eIF4F / mTOR)
Shares MYC, PIK3CA / PI3K-alpha, PI3K / AKT / mTOR, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayCircadian control
Shares MYC, Abramson Cancer Center, University of Pennsylvania, Memorial Sloan Kettering Cancer Center, Cytotoxic chemotherapy and the tag mechanism.
- PathwayEpigenetic reprogramming
Shares Vorasidenib, IDH1 / IDH2, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayNotch signalling
Shares MYC, Abramson Cancer Center, University of Pennsylvania and the tag mechanism.
- PathwayJAK–STAT signalling
Shares Cancer cachexia, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayRNA splicing
Shares MYC, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayCancer neuroscience (nerve–tumour signalling)
Shares MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center and the tag mechanism.
- PathwayInflammation & NF-κB
Shares Cancer cachexia, Memorial Sloan Kettering Cancer Center and the tag mechanism.