Cachexia signals
Tumours send hormones (GDF-15, IL-6) that switch off appetite and melt muscle and fat. Cachexia kills a fifth of patients directly and stops treatment in many more; the first drugs against it are now in phase 3.
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 thermostat hijacked by the tumour: it tells the body it is full when it is starving and orders the furnace to burn muscle for fuel. Ponsegromab cuts the wire to the thermostat.
What happens
In plain words, then the glossary entries the stage rests on. Chapter 8, The tumour ecosystem: A tumour is a corrupted organ: cancer cells plus the fibroblasts, matrix, vessels, nerves, microbes and immune cells they recruit, and the signals they send to the rest of the body.
Tumours send hormones (GDF-15, IL-6) that switch off appetite and melt muscle and fat. Cachexia kills a fifth of patients directly and stops treatment in many more; the first drugs against it are now in phase 3.
Cancer cachexia. The wasting syndrome that kills up to a third of cancer patients: tumours send hormonal signals (GDF-15, IL-6) that switch off appetite and burn muscle and fat. The first drug to reverse it, ponsegromab, showed weight gain in 2024.
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.
No target record is listed at this stage or drawn in its diagrams; the pathways above carry the mechanism.
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.
No product in the corpus acts on a target at this stage yet.
How tumours escape
Records tied to this stage that describe resistance, evasion or tolerance. The resistance atlas lists the routes class by class.
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.
- Does GDF-15 blockade (ponsegromab) extend life or only weight?
- Can cachexia be prevented rather than treated?
- being tested at scaleclinicFour weeks of training and nutrition before major cancer surgery, as standard
Getting fitter and better nourished before an operation reduces complications and speeds recovery. It is cheap, but only a few hospitals do it.
- early clinicalclinicA cheap old tablet to restore appetite
A low dose of an old, inexpensive tablet improved appetite and weight in a randomised trial of people with advanced cancer. It could be used almost everywhere tomorrow.
- early clinicalclinicA dietitian in every gastrointestinal and head and neck tumour board
Malnutrition is the commonest untreated complication in cancers of the gut, throat and pancreas. Putting a dietitian in the meeting where treatment is decided means it is seen and treated before chemotherapy starts, not after weight has been lost.
- early clinicalindustryCombine the new anti-wasting antibody with exercise and protein
A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it.
- early clinicalresearchConfirm low-dose olanzapine for appetite and weight in advanced cancer worldwide
A randomised placebo-controlled trial at Tata Memorial found that 2.5 mg of olanzapine daily, a cheap antipsychotic pill already used for chemotherapy nausea, improved appetite and weight gain in patients starting chemotherapy for advanced stomach, lung and hepatopancreatobiliary cancers. A multinational confirmatory trial is needed before guidelines and labels adopt it.
- early clinicalregulatorGet the one approved appetite drug licensed beyond a single country
A drug that improves appetite and lean weight in cancer wasting is approved in Japan but almost nowhere else. Reviewing the existing evidence could widen access quickly.
- early clinicalpayerPay for supervised exercise the way we pay for drugs
A large trial showed a structured exercise programme improved survival after bowel cancer. Almost no health system pays for it, so almost no patient gets it.
- early clinicalindustryTreat cachexia as a disease: GDF-15 blockade plus anabolic and nutrition bundles
The wasting that kills many cancer patients has had no effective drug. New antibodies against GDF-15 restored weight in early trials. Combine them with exercise and nutrition and test properly.
- early clinicalTreat cachexia before it starts
Cachexia, the muscle wasting driven partly by the hormone GDF-15, kills cancer patients and stops chemotherapy being completed, and late muscle loss is largely irreversible. Ponsegromab, an anti-GDF-15 antibody, reversed weight loss in established cachexia in 2024; the next test is a phase 3 giving it from first-line chemotherapy in pancreatic cancer to prevent wasting rather than treat it.
- preclinical evidencedataRead muscle loss automatically from scans patients already have
Every staging scan contains a precise measure of muscle mass that nobody looks at. Software could report it automatically and flag patients heading for wasting.
9 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.
- 2020reviewManagement of Cancer Cachexia: ASCO GuidelineJournal of Clinical Oncology
- 2011reviewDefinition and classification of cancer cachexia: an international consensusThe Lancet Oncology
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 8.5 of 56.