Regorafenib
Stivarga
Multi-kinase inhibitor (VEGFR/KIT/PDGFR/FGFR/RAF)
Evidence Score
58
Broad-spectrum kinase inhibitor targeting VEGFR1-3, KIT, PDGFR, FGFR, and RAF. FDA-approved for GIST after imatinib and sunitinib failure. Covers multiple pathway nodes relevant to SDH-deficient tumors.
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 (third-line)
- Metastatic colorectal cancer
- Hepatocellular carcinoma
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.