EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype
A partir de données portant sur 383 échantillons tumoraux prélevés sur des patients atteints d'un carcinome invasif de la vessie, puis menée sur des lignées cellulaires et un modèle murin, cette étude française identifie un sous-type de la maladie défini par l'expression de 40 gènes, puis montre que ce sous-type est sensible à une thérapie ciblée anti EGFR
Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with a poor outcome. Molecular stratification of MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series of large-scale transcriptomic data (383 tumors), we identified an MIBC subgroup accounting for 23.5% of MIBC, associated with shorter survival and displaying a basal-like phenotype, as shown by the expression of epithelial basal cell markers. Basal-like tumors presented an activation of the epidermal growth factor receptor (EGFR) pathway linked to frequent EGFR gains and activation of an EGFR autocrine loop. We used a 40-gene expression classifier derived from human tumors to identify human bladder cancer cell lines and a chemically induced mouse model of bladder cancer corresponding to human basal-like bladder cancer. We showed, in both models, that tumor cells were sensitive to anti-EGFR therapy. Our findings provide preclinical proof of concept that anti-EGFR therapy can be used to target a subset of particularly aggressive MIBC tumors expressing basal cell markers and provide diagnostic tools for identifying these tumors.