Specific features of ß-catenin-mutated hepatocellular carcinomas
Cet article résume les avancées récentes en matière de classification des carcinomes hépatocellulaires, présente les mécanismes de régulation impliqués dans la stabilisation de la bêta caténine, l'activité transcriptionnelle et la liaison aux protéines partenaires, décrit les caractéristiques phénotypiques des carcinomes hépatocellulaires avec gène CTNNB1 muté, examine les approches thérapeutiques ciblant les tumeurs hépatiques avec mutation de la bêta caténine puis identifie les perspectives d'innovation
CTNNB1, encoding the ß-catenin protein, is a key oncogene contributing to liver carcinogenesis. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer in adult, representing the third leading cause of cancer-related death. Aberrant activation of the Wnt/ß-catenin pathway, mainly due to mutations of the CTNNB1 gene, is observed in a significant subset of HCC. In this review, we first resume the major recent advances in HCC classification with a focus on CTNNB1-mutated HCC subclass. We present the regulatory mechanisms involved in β-catenin stabilisation, transcriptional activity and binding to partner proteins. We then describe specific phenotypic characteristics of CTNNB1-mutated HCC thanks to their unique gene expression patterns. CTNNB1-mutated HCC constitute a full-fledged subclass of HCC with distinct pathological features such as well-differentiated cells with low proliferation rate, association to cholestasis, metabolic alterations, immune exclusion and invasion. Finally, we discuss therapeutic approaches to target ß-catenin-mutated liver tumours and innovative perspectives for future drug developments.
British Journal of Cancer , article en libre accès, 2024