Sunitinib
Sutent
Multi-kinase inhibitor (VEGFR/PDGFR/KIT)
Evidence Score
75
Inhibits multiple receptor tyrosine kinases including VEGFR1/2/3, PDGFR-α/β, KIT, FLT3, and RET. Blocks angiogenesis and has direct anti-tumor effects. Used as standard therapy in advanced GIST and has shown activity in SDH-deficient GIST and paraganglioma.
Downstream of HIF activation, VEGF/VEGFR2 signaling drives tumor angiogenesis — the formation of new blood vessels that supply the tumor with oxygen and nutrients.
Upstream event:
HIF-mediated VEGFA transcriptional activation
Downstream effects:
Metabolic reprogramming from SDH loss activates the PI3K/AKT/mTOR signaling axis, promoting cell growth, proliferation, and survival. Multiple upstream inputs converge on mTOR.
Upstream event:
HIF-mediated growth factor signaling + metabolic stress + AMPK dysregulation
Downstream effects:
KDR
VEGF receptor 2 (VEGFR2)
Primary VEGF receptor on endothelial cells. Target of sunitinib, regorafenib, and other multi-kinase inhibitors.
UniProt: P35968
KIT
KIT proto-oncogene receptor tyrosine kinase
Primary oncogene in most GISTs, but SDH-deficient GISTs typically have wild-type KIT. Some residual KIT signaling may persist.
UniProt: P10721
Approved Indications
- Advanced GIST (after imatinib failure)
- Advanced renal cell carcinoma
- Pancreatic neuroendocrine tumors
Evidence from PubMed, OpenTargets, and ChEMBL will appear here once external data integration is enabled.
Coming in Phase 3
Have Claude analyze this drug's repurposing potential for SDH-deficient diseases.