EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype

• DOI: 10.1126/scitranslmed.3008970
• Publication Date: 2014-07-09T20:37:19Z
• Authors: Sandra Rebouissou; Isabelle Bernard-...; Aurélien de Reyniès; May-Linda Lepage; Clémentine Krucker; Elodie Chapeaublanc; Aurélie Hérault; Aurélie Kamoun; Aurélie Caillault; Eric Letouzé; Nabila Elarouci; Yann Neuzillet; Yves Denoux; Vincent Molinié; Dimitri Vordos; Agnès Laplanche; Pascale Maillé; Pascale Soyeux; Karina Ofualuka; Fabien Reyal; Anne Biton; Mathilde Sibony; Xavier Paoletti; Jennifer Southgate; Simone Benhamou; Thierry Lebret; Yves Allory; François Radvanyi
• Keywords: Basal (medicine)

Muscle-invasive bladder carcinoma (MIBC) constitutes a heterogeneous group of tumors with poor outcome. Molecular stratification MIBC may identify clinically relevant tumor subgroups and help to provide effective targeted therapies. From seven series large-scale transcriptomic data (383 tumors), we identified an subgroup accounting for 23.5% MIBC, associated shorter survival displaying basal-like phenotype, as shown by the expression epithelial basal cell markers. Basal-like presented activation epidermal growth factor receptor (EGFR) pathway linked frequent EGFR gains autocrine loop. We used 40-gene classifier derived from human cancer lines chemically induced mouse model corresponding cancer. showed, in both models, that cells were sensitive anti-EGFR therapy. Our findings preclinical proof concept therapy can be target subset particularly aggressive expressing markers diagnostic tools identifying these tumors.