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

Sandra Rebouissou, Isabelle Bernard-Pierrot, 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 ReyalAnne Biton, Mathilde Sibony, Xavier Paoletti, Jennifer Southgate, Simone Benhamou, Thierry Lebret, Yves Allory, François Radvanyi

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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.

Original languageEnglish
Article number244ra91
Number of pages11
JournalScience Translational Medicine
Issue number244
Publication statusPublished - 9 Jul 2014

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