O SMO ativa a mutação (Luxado)
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| ID | BIO-SMO |
|---|---|
| Tipo | Biomarcador |
| Alegais | SMO mutationАктивуюча мутація SMO (Smoothened) |
| Estado | reviewed 2026-05-04 | pending_clinical_signoff |
| Doenças | DIS-BCC |
| Fontes | SRC-ESMO-SARCOMA-2024 SRC-NCCN-SKIN-2025 |
Fatos de biomarcadores
| Tipo de biomarcador | gene_mutation |
|---|---|
| Detalhes da mutação | {"exon": "multiple", "functional_impact":"activando", "gene": SMO, "variant_type":", "missense activando"} |
| Medição | MétodoPanel NGS tumoral (com base em ADN); variantes comuns: W535L, L412F, Q477E, S533N |
| Procura de ação | {"gene": "SMO", "variant": "activating_mutation"} |
| Biomarcadores relacionados | BIO-PTCH1 |
Notas
SMO (Smoothened) is a G-protein-coupled receptor that transmits Hedgehog (HH) signaling. Normally suppressed by PTCH1; activated when PTCH1 loses its inhibitory function (whether via PTCH1 loss-of-function or SMO gain-of-function mutation). SMO activating mutations (~10–20% of BCCs) and PTCH1 loss-of-function (~90% of BCCs) both result in constitutive HH pathway activation. Vismodegib and sonidegib are SMO antagonists — they bind the SMO transmembrane domain and block downstream HH signaling (GLI1/2 repression). In practice, BCC HHI therapy does not require pre-testing for SMO vs PTCH1 mutation — all BCCs have HH pathway activation. SMO mutations also occur in sporadic medulloblastoma (SHH subtype) and rarely in other tumors. Resistance: secondary SMO mutations (D473H most common) emerge during vismodegib therapy, driving acquired resistance. Sonidegib may be active in some vismodegib-resistant D473H mutants.
Usado por
Relevância terapêutica
BMA-SMO-BCC- Inibidores da via Hedgehog (HH) — vismodegib (Erivedge, FDA 2012) e sonidegib (Odomzo,...
Biomarcador
BIO-PTCH1- mutação da perda de função do PTCH1 (Patched-1)
Doença
DIS-BCC- Carcinoma de células basocelulares (BCC)
Indicação
IND-BCC-1L-SONIDEGIB- IND-BCC-1L-SONIDEGIB