Glutamine
The tumour's second favourite food: it feeds the energy cycle, donates nitrogen for DNA letters, and makes antioxidants. MYC- and KRAS-driven cancers eat so much that the T cells next door go hungry.
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 construction site that runs on two deliveries: sand (glucose) for bulk and steel (glutamine) for the frame and the rebar. MYC doubles the steel order. Cutting one delivery rarely stops the build because the site switches suppliers; that is why single metabolic drugs have disappointed.
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.
The tumour's second favourite food: it feeds the energy cycle, donates nitrogen for DNA letters, and makes antioxidants. MYC- and KRAS-driven cancers eat so much that the T cells next door go hungry.
Glutamine addiction. After glucose, glutamine is the tumour's favourite food. It feeds the energy cycle, donates nitrogen for making DNA letters, and makes the antioxidant glutathione. MYC- and KRAS-driven cancers eat so much of it that they starve the T cells next door.
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.
KRAS is the most commonly mutated cancer gene, called 'undruggable' for 40 years until 2021.
A metabolic enzyme whose mutant form produces a molecule that scrambles how genes are read; blocking it slows brain tumours and leukaemias.
PD-1 is a brake on T cells. Blocking it releases the immune system against the tumour and has cured some previously incurable cancers.
AKT is a central survival kinase downstream of PI3K, blocked by capivasertib in breast and now prostate cancer.
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.
- AdagrasibApprovedNon-small-cell lung cancerColorectal cancerPancreatic ductal adenocarcinoma
- Avutometinib + defactinibApprovedOvarian cancerLow-grade serous ovarian cancer
- DaraxonrasibApprovedPancreatic ductal adenocarcinomaMetastatic pancreatic ductal adenocarcinomaKRAS G12C-mutant pancreatic ductal adenocarcinoma
- FulzerasibApprovedNon-small-cell lung cancer
- GarsorasibApprovedNon-small-cell lung cancerKRAS G12C-mutant non-small-cell lung cancer
- GlecirasibApprovedNon-small-cell lung cancerKRAS G12C-mutant non-small-cell lung cancer
- Guardant360 CDxApprovedNon-small-cell lung cancerHR-positive / HER2-negative breast cancer
- Resolution ctDx FIRSTApprovedNon-small-cell lung cancer
- +16 more at KRAS →
- EnasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemiaSinonasal undifferentiated carcinoma (SNUC) and SWI/SNF-deficient sinonasal carcinoma
- IvosidenibApprovedAcute myeloid leukaemiaBiliary tract cancer (cholangiocarcinoma)IDH1- and IDH2-mutated acute myeloid leukaemia
- OlutasidenibApprovedAcute myeloid leukaemiaIDH1- and IDH2-mutated acute myeloid leukaemia
- Oncomine Dx Target TestApprovedNon-small-cell lung cancerBiliary tract cancer (cholangiocarcinoma)
- VorasidenibApprovedGlioma & glioblastomaAstrocytoma, IDH-mutant (grades 2 to 4)Oligodendroglioma, IDH-mutant and 1p/19q-codeleted
- HMPL-306Phase 3
- SafusidenibPhase 3
- TQB3454Phase 3
- CadonilimabApprovedCervical cancerGastric & gastro-oesophageal junction cancer
- CamrelizumabApprovedOesophageal cancerHepatocellular carcinomaNon-small-cell lung cancer
- Camrelizumab + rivoceranibApprovedHepatocellular carcinoma
- CemiplimabApprovedNon-small-cell lung cancerMelanomaPD-L1-high non-small-cell lung cancer without a driver mutation
- DostarlimabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaEndometrial cancerColorectal cancer
- IvonescimabApprovedNon-small-cell lung cancerColorectal cancerTriple-negative breast cancer (TNBC)
- NivolumabApprovedMelanomaNon-small-cell lung cancerRenal cell carcinoma
- PembrolizumabApprovedMismatch repair deficient (MSI-high) pancreatic ductal adenocarcinomaTriple-negative breast cancer (TNBC)Non-small-cell lung cancer
- +23 more at PD-1 →
- CapivasertibApprovedHR-positive / HER2-negative breast cancerProstate cancerMetastatic hormone-sensitive prostate cancer
- EverolimusApprovedHR-positive / HER2-negative breast cancerRenal cell carcinomaNeuroendocrine tumours
- GedatolisibApprovedHR-positive / HER2-negative breast cancerHR-positive metastatic breast cancer after CDK4/6 inhibitors
- IpatasertibPhase 3
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
- early clinicalindustryAdd the second drug on day one when the escape route is predictable
If most tumours escape a drug by the same back-up route, blocking that route from the start may prevent resistance rather than chase it.
- preclinical evidenceresearchLook for the resistant sub-population before the first dose
Resistance mutations often exist in a tiny fraction of cells before treatment starts. Error-corrected sequencing that detects variants below 0.01 percent allele fraction could find them at diagnosis and prompt a mechanism-matched combination from day one.
- 2023rctCodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancerNew England Journal of Medicinechanged practice
Measured by
Biomarkers, tests and assays in the corpus that read this stage in a patient.
- therascreen KRAS RGQ PCR KitPCR
- FoundationOne CDxNGS tissue
- Guardant360 CDxNGS plasma
- Agilent Resolution ctDx FIRSTNGS plasma
- Abbott RealTime IDH1PCR
- Abbott RealTime IDH2PCR
- PD-L1 IHC 22C3 pharmDxIHC
- PD-L1 IHC 28-8 pharmDxIHC
- VENTANA MMR RxDx PanelIHC
- MSI by PCR (Promega MSI Analysis System and equivalents)PCR
- Tumour mutational burden (FoundationOne CDx and equivalents)NGS tissue
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.
- Can glutamine be blocked in tumour cells while sparing T cells (DRP-104 concept)?
- Which tumours are truly glutamine-addicted in patients rather than in dishes?
- early clinicalindustryAn open-science consortium on the undruggable drivers, open until a candidate
Companies and public funders would pool money and scientists to crack the hardest cancer proteins, such as MYC and mutant p53, sharing everything openly until there is a real drug candidate, then competing on the final product.
- early clinicalindustryCovalent chemistry for the RAS mutations that still have no drug
One RAS mutation can now be drugged because it offers a reactive handle. Most RAS mutations do not, so new chemistry is needed to grab other amino acids.
- 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 clinicalMaking microsatellite-stable colorectal cancer immunotherapy-responsive
Ninety-five percent of bowel cancers ignore immunotherapy. Combinations that heat the tumour up (targeted drugs, radiation, new checkpoints) are the main hope.
- early clinicalOff-the-shelf KRAS vaccines after pancreatic cancer surgery
Almost every pancreatic cancer shares one of a handful of KRAS mutations. A pre-made vaccine against them could be given to every patient after surgery.
- early clinicalRAS(ON) inhibitors to convert unresectable pancreatic cancer to resectable
If daraxonrasib shrinks metastatic tumours this well, use it before surgery to make more locally advanced tumours operable.
- preclinical evidenceresearchA synthetic lethality map for every cancer driver in every tissue context
For each cancer-causing mutation, find every gene the cancer cell newly depends on, in every tissue, so that even undruggable drivers get druggable partners.
- preclinical evidenceresearchAn open degrader consortium against every undruggable driver transcription factor
Cancer's most important drivers, such as MYC and mutant p53, cannot be blocked with normal drugs. Pool effort and share results openly to build molecules that destroy them instead.
- preclinical evidenceindustryAntibodies that see mutant KRAS and p53 fragments displayed on the cell surface
Cells chop up their internal proteins and display the pieces on their surface. That means even undruggable proteins inside the cell can be attacked from outside by the immune system.
- preclinical evidenceengineeringSelf-driving laboratories that run the cancer biology hypothesis loop autonomously
Robotic labs guided by AI that design experiments on tumour models, run them, read the results and design the next ones, around the clock, with every result published openly.
3 more ideas are linked to this stage's pathways, targets and terms; see the rankings →
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2026reviewKRYSTAL-12 plain language summary: adagrasib for non-small-cell lung cancer with KRAS G12C mutationsFuture Oncology
- 2023rctCodeBreaK 200: sotorasib versus docetaxel in KRAS G12C-mutated lung cancer, a modest win for the first KRAS drugThe Lancetchanged practice
- 2023rctCodeBreaK 300: sotorasib plus panitumumab in chemotherapy-refractory KRAS G12C colorectal cancerNew England Journal of Medicinechanged practice
- 2023rctINDIGO: vorasidenib, the first targeted drug for IDH-mutant low-grade gliomaNew England Journal of Medicinechanged practice
- 2021reviewFDA's Project Optimus manifesto: cancer drugs are approved at doses that are too highNew England Journal of Medicinechanged practice
- 2017translationalRecurrent IDH2 R172X mutations in sinonasal undifferentiated carcinomaModern Pathologychanged practice
- 2016reviewFrom Krebs to clinic: glutamine metabolism to cancer therapyNature Reviews Cancer
- 2013reviewCancer genome landscapes: about 140 driver genes, and each tumour needs only a handfulScience
- 2013basicOstrem and Shokat: the hidden pocket that made KRAS G12C druggableNature
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 5.2 of 56.