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Erdafitinib
Balversa
Pan-FGFR inhibitor (FGFR1/2/3/4), FDA-approved
Evidence Score
42
Orally bioavailable, selective pan-FGFR inhibitor (FGFR1-4). FDA-approved for FGFR2/3-altered urothelial carcinoma — the first approved FGFR-targeted therapy. The mechanistic rationale for SDH-deficient tumors is the same as rogaratinib: succinate-driven DNA hypermethylation disrupts insulators at the FGF3/FGF4 locus, generating aberrant FGF ligands that activate FGFR1 in an autocrine loop. Erdafitinib inhibits FGFR1 (IC50 ~1.2 nM) and is therefore expected to interrupt this signaling cascade. No SDH-deficient-specific clinical data yet, but as an FDA-approved drug with a defined FGFR1 target mechanism it may be more accessible than rogaratinib in countries where rogaratinib is not available. The Phase 2 rogaratinib trial (PMID 42191879) provides the mechanistic validation, and the FGFR alterations targeted in SDH-GIST overlap with erdafitinib's pharmacological profile. Erdafitinib should be considered an alternative FGFR inhibitor pending dedicated SDH-GIST clinical data.
SDH-loss-driven genome-wide DNA hypermethylation disrupts CTCF-binding insulator elements flanking the FGF3/FGF4 gene locus, causing aberrant, high-level transcription of these oncogenic FGF ligands. The ligands activate an autocrine/paracrine FGFR1 signaling loop that promotes SDH-deficient tumor growth. This mechanism was established in GIST by a 2026 Phase 2 trial of rogaratinib (Nat Med 2026, PMID 42191879).
Upstream event:
Succinate-driven TET inhibition → genome-wide DNA hypermethylation → CTCF insulator disruption → aberrant FGF3/FGF4 activation
Downstream effects:
FGFR1
Fibroblast growth factor receptor 1
Receptor tyrosine kinase that mediates FGF3/FGF4 signaling. In SDH-deficient GIST, aberrant FGF3/FGF4 overexpression driven by DNA-hypermethylation-induced insulator disruption activates FGFR1 in an autocrine loop. Target of rogaratinib (pan-FGFR inhibitor) in the Phase 2 trial showing 41.7% ORR (Nat Med 2026, PMID 42191879).
UniProt: P11362
FGFR2
Fibroblast growth factor receptor 2
Second FGFR subtype co-expressed in SDH-deficient tumors; pan-FGFR inhibitors including rogaratinib and erdafitinib target FGFR1-4. Inhibited by rogaratinib in the SDH-deficient GIST Phase 2 trial and by erdafitinib (FDA-approved pan-FGFR, urothelial carcinoma).
UniProt: P21802
Approved Indications
- Locally advanced or metastatic urothelial carcinoma with FGFR2/3 alterations
Evidence from PubMed, OpenTargets, and ChEMBL will appear here once external data integration is enabled.
Coming in Phase 3
For research exploration only — not medical advice. Consult your doctor before acting on any information.
Have Claude analyze this drug's repurposing potential for SDH-deficient diseases.