Lipids
Dividing cells need membranes, and membranes are fat. Cancers switch on fat-building enzymes adults normally keep off and steal lipids from nearby fat cells, which links obesity to thirteen cancers.
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 must build its own walls. Normal adult tissue buys wall panels from a supplier (dietary fat); cancer reopens its own panel plant (FASN) and, when it lands in a fat depot, simply strips panels off the buildings next door.
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.
Dividing cells need membranes, and membranes are fat. Cancers switch on fat-building enzymes adults normally keep off and steal lipids from nearby fat cells, which links obesity to thirteen cancers.
Lipid synthesis, uptake & cholesterol. Dividing cells need membranes, and membranes are fat. Cancers switch on the fat-building enzymes most adult tissues keep off, and in fatty environments (breast, omentum, bone marrow) they also steal lipids from neighbouring fat cells. This links obesity to cancer and offers new drug targets.
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.
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 →
- 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.
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 GLP-1 agonists lower cancer incidence beyond their effect on weight?
- Will FASN or SCD1 inhibitors find a tumour type where they matter?
- early clinicalresearchA dose-finding trial for exercise after cancer
CHALLENGE proved exercise works in colon cancer but not how much is needed. A trial comparing doses, as we would for a drug, would tell health systems what to fund.
- early clinicaldataLink bariatric and GLP-1 registries to cancer registries in every country that has both
Millions of people have had weight-loss surgery or now take weight-loss drugs. Linking those records to cancer registries would show, cancer by cancer, how much reversing obesity prevents, for almost no cost.
- speculativeindustryGLP-1 receptor agonists as adjuvant weight-loss therapy in HR-positive breast cancer
Coaching-based weight loss did not clearly cut breast cancer recurrence in BWEL, perhaps because the weight loss was too small. Drugs that produce three times as much weight loss could settle whether weight itself matters.
Key evidence
Papers in the corpus tied to this stage's pathways, targets and terms, newest first.
- 2016reviewThe multifaceted roles of fatty acid synthesis in cancerNature Reviews Cancer
- 2003observationalCalle 2003: overweight, obesity and death from cancer in 900,000 US adultsNew England Journal of Medicine
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 5.3 of 56.