What is GIST?
GIST stands for gastrointestinal stromal tumour — a rare type of tumour that grows in the wall of the digestive tract, most often the stomach or small intestine. It arises from specialised "pacemaker" cells that help move food through the gut.
Most GISTs are driven by a fault in one of two genes, KIT or PDGFRA. That discovery was a medical success story: targeted drugs such as imatinib were designed to switch those faulty genes off, and they transformed outcomes for the majority of GIST patients.
What is SDH-deficient GIST?
SDH-deficient GIST is a distinct, much rarer subtype — estimated to make up only a small fraction of all GISTs. Crucially, it is not driven by the usual KIT or PDGFRA faults. Instead, it is caused by the loss of an enzyme complex called succinate dehydrogenase (SDH).
SDH is part of the cell's energy machinery. When it stops working, the cell's chemistry is thrown off in ways that can drive cancer — a completely different mechanism from ordinary GIST. That difference matters enormously, because it means the front-line drugs that work so well for common GIST tend to work poorly here. Patients with this subtype are, in effect, left without the treatment that helped everyone else.
Who does it affect?
SDH-deficient GIST stands out because of who it tends to strike. Unlike common GIST, which usually appears in older adults, this subtype most often affects children and young adults, and is seen more frequently in females. It typically arises in the stomach, and can be multifocal — meaning more than one tumour at once.
It often behaves more slowly than common GIST, but it can still spread (most commonly to the liver or nearby lymph nodes), and it can persist for many years — which is exactly why better long-term treatment options are so needed.
Symptoms
Symptoms are not specific to this subtype and can be easy to miss. They may include:
- Vague abdominal pain or discomfort, or a feeling of fullness.
- Anaemia or fatigue, sometimes from slow bleeding into the gut.
- Nausea, or a lump that a doctor can feel.
- In some cases, no symptoms at all — the tumour is found incidentally on a scan done for another reason.
Because these signs are common to many conditions, a firm answer only comes from proper investigation and specialist review.
How it's diagnosed
Diagnosis usually involves imaging (such as a CT or MRI scan), a biopsy, and — importantly for this subtype — specialised laboratory testing. A pathologist can run a stain that reveals whether the SDH enzyme is present or lost, and genetic testing can identify changes in the SDH genes. Getting this right matters: because SDH-deficient GIST looks similar to common GIST under the microscope, it can be missed unless the specific tests are done.
How it's treated
Surgery to remove the tumour is the cornerstone of treatment. Beyond that, the picture is harder: the standard targeted drugs for common GIST are generally much less effective against this subtype. Some patients are offered other multi-target drugs, and researchers are actively studying newer approaches aimed squarely at the biology of SDH loss — including strategies drawn from metabolism and immunotherapy.
This is precisely the gap Mission Pegasus works in: taking the most promising scientific leads and pushing them toward real, tested treatment options.
Is it hereditary?
Sometimes. A meaningful proportion of SDH-deficient GISTs are linked to an inherited change in one of the SDH genes, which can also be associated with certain other rare tumours. For that reason, genetic counselling and testing are often recommended — both for the patient and, where relevant, for family members. Other cases arise from changes that are not inherited. A specialist can explain what testing makes sense in each situation.
Why research matters
SDH-deficient GIST sits in a difficult spot: it is too rare to attract large, dedicated drug-development programmes, yet different enough that the existing treatments don't serve it well. Progress depends on connecting and testing the scientific leads that already exist — and doing it with urgency. That focused, catalytic work is the whole purpose of Mission Pegasus.