Also see Clinical Trials
Because the KIT protein is activated in most Pediatric GISTs, it remains a therapeutic target. Gleevec is a poor inhibitor of wild-type GIST. More potent inhibitors of wild-type KIT, such as Tasigna (also known as nilotinib or AMN107) or Sutent (also known as sunitinib or SU11248) may be more effective.
See Activated KIT in wild-type GIST remains a target
In addition, recent research suggests that another protein, insulin-like growth factor receptor 1 (IGF-1R) may also be important in wild-type and Pediatric GIST.
See New target found for wild-type and Pediatric GIST (IGR-1R) and
Potential new signal pathway in GIST (IGF-1R)
NOTE: There is some clinical evidence that KIT inhibitors can have a beneficial effect in Pediatric GIST. At this time the hypothesis that IGR-1R inhibitors will have a benefical effect is based on lab experiments and needs verification in clinical trials. It remains to be seen which of these therapies will be more important. It is possible that inhibition of both pathways may be more effective than inhibition of either by itself.
In Familial Paraganglioma and Gastric Stromal Sarcoma, the mutations in the succinate dehydrogenase gene suggest other therapeutic strategies may be required or beneficial. Some potential candidates include HIF1 a inhibitors (in trials) and derivatives of a ketoglutarate or dichloroacetate (DCA). The benefits of these type drugs for other Pediatric GIST patients, including Carney’s Triad, is less clear. The clinical experience of 3 patients with paragangliomas, (2 with germline defects) suggests that Sutent (sunitinib) might have activity against paragangliomas. Sutent has also shown activity against pediatric GIST is a small series of patients.
See Rationale and evidence for for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma (MPP)
Another case report involves a "Patient with Malignant Paraganglioma Responding to the Multikinase Inhibitor Sunitinib Malate". While this patient responded initially, the patient developed progressive shortness of breath after 16 weeks on sunitinib and subsequently died.
See Carney-Stratakis Syndrome