TY - JOUR
T1 - EGFR as a potential therapeutic target for a subset of muscle-invasive bladder cancers presenting a basal-like phenotype
AU - Rebouissou, Sandra
AU - Bernard-Pierrot, Isabelle
AU - de Reyniès, Aurélien
AU - Lepage, May-Linda
AU - Krucker, Clémentine
AU - Chapeaublanc, Elodie
AU - Hérault, Aurélie
AU - Kamoun, Aurélie
AU - Caillault, Aurélie
AU - Letouzé, Eric
AU - Elarouci, Nabila
AU - Neuzillet, Yann
AU - Denoux, Yves
AU - Molinié, Vincent
AU - Vordos, Dimitri
AU - Laplanche, Agnès
AU - Maillé, Pascale
AU - Soyeux, Pascale
AU - Ofualuka, Karina
AU - Reyal, Fabien
AU - Biton, Anne
AU - Sibony, Mathilde
AU - Paoletti, Xavier
AU - Southgate, Jennifer
AU - Benhamou, Simone
AU - Lebret, Thierry
AU - Allory, Yves
AU - Radvanyi, François
N1 - Copyright © 2014, American Association for the Advancement of Science.
PY - 2014/7/9
Y1 - 2014/7/9
N2 - 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.
AB - 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.
U2 - 10.1126/scitranslmed.3008970
DO - 10.1126/scitranslmed.3008970
M3 - Article
C2 - 25009231
SN - 1946-6234
VL - 6
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 244
M1 - 244ra91
ER -