Les mutations somatiques de la perte de fonction APC se produisent chez environ 80% des carcinomes colorrectaux sporadiques (C...
Vue déterministe de l'entité source de la LJAM. L'autorité clinique demeure avec les ID de la source cités et l'état d'approbation de l ́examinateur.
| ID | BMA-APC-CRC |
|---|---|
| Type | Pertinence thérapeutique |
| État | reviewed 2026-05-04 | pending_clinical_signoff | actionability review required |
| Maladies | DIS-CRC |
| Sources | SRC-ESMO-CRC-2024 SRC-NCCN-COLON-2025 |
Faits relatifs à l ' action en justice
| Biomarqueur | BIO-APC |
|---|---|
| Variante | APC loss-of-function mutation (somatic) in colorectal carcinoma — WNT/β-catenin pathway driver; no approved APC-directed therapy |
| Maladie | DIS-CRC |
| Niveau ESCAT | IIIB |
| Combinaisons recommandées | FOLFOX or FOLFIRI ± bevacizumab — standard 1L mCRC regardless of APC status (NCCN Category 1), Cetuximab or panitumumab — for RAS/RAF wild-type left-sided mCRC (anti-EGFR eligibility determined by KRAS/NRAS/BRAF, not APC), Pembrolizumab 200 mg q3w — 1L for MSI-H/dMMR mCRC (KEYNOTE-158/177; APC co-mutation common but not the eligibility criterion) |
| Résumé des faits | APC somatic loss-of-function mutations occur in ~80% of sporadic colorectal carcinomas (CRC) and represent the earliest molecular event in the adenoma-carcinoma sequence. APC loss stabilizes β-catenin, driving constitutive WNT target gene transcription (MYC, CCND1). Despite its ubiquity, APC is not a direct therapeutic target for systemic therapy in CRC: (1) WNT pathway inhibitors: porcupine inhibitors (WNT-974/LGK-974, RXC004) block Wnt ligand secretion upstream of APC and are in Phase I/II trials across WNT-driven tumors including CRC. Early results show modest single-agent activity; no CRC-specific approval. (2) Tankyrase inhibitors: block AXIN degradation → restore destruction complex despite APC loss; early preclinical/Phase I (NVP-TNKS656, G007-LK); dose-limiting GI toxicity. (3) APC loss does not predict response to anti-EGFR (cetuximab/panitumumab) in CRC — RAS/RAF wild-type status determines anti-EGFR eligibility, not APC status. (4) MSI-H/dMMR CRC (~15%) frequently co-occurs with somatic APC mutation; immunotherapy (pembrolizumab 1L or 2L) is actionable via the MMR deficie... |
Notes
ESCAT IIIB: APC mutation marks the adenoma-carcinoma sequence but is not currently actionable for therapy selection. Key clinical implications: (1) Germline testing: any patient <50y with CRC or with ≥10 adenomas should have germline APC testing to exclude FAP/AFAP; prophylactic colectomy is curative. (2) WNT pathway state: nuclear β-catenin IHC is a surrogate; useful when full sequencing unavailable but does not add actionability above sequencing. (3) Trial eligibility: WNT pathway basket trials (porcupine inhibitors RXC004, LGK-974) use APC mutation or CTNNB1 mutation as eligibility criteria. (4) Resistance context: APC loss in CRC that acquires KRAS or BRAF mutations represents late clonal evolution; serial ctDNA may track this.
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