The road to resistance: EGFR mutation and cetuximab

Andrea Bertotti, Giorgia Migliardi, Francesco Galimi, Francesco Sassi, Davide Torti, Claudio Isella, Davide Corà, Federica Di Nicolantonio, Michela Buscarino, Consalvo Petti, Dario Ribero, Nadia Russolillo, Andrea Muratore, Paolo Massucco, Alberto Pisacane, Luca Molinaro, Emanuele Valtorta, Andrea Sartore-Bianchi, Mauro Risio, Lorenzo Capussotti, Marcello Gambacorta, Salvatore Siena, Enzo Medico, Anna Sapino, Silvia Marsoni, Paolo M Comoglio, Alberto Bardelli, Livio Trusolino, None, A molecularly annotated platform of patient-derived xenografts ("xenopatients") identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer. Cancer Discovery. ,vol. 1, pp. 508- 523 ,(2011) , 10.1158/2159-8290.CD-11-0109

C Li, M Iida, E F Dunn, A J Ghia, D L Wheeler, Nuclear EGFR contributes to acquired resistance to cetuximab. Oncogene. ,vol. 28, pp. 3801- 3813 ,(2009) , 10.1038/ONC.2009.234

Pasi A. Jänne, Nathanael Gray, Jeff Settleman, Factors underlying sensitivity of cancers to small-molecule kinase inhibitors Nature Reviews Drug Discovery. ,vol. 8, pp. 709- 723 ,(2009) , 10.1038/NRD2871

Clara Montagut, Alba Dalmases, Beatriz Bellosillo, Marta Crespo, Silvia Pairet, Mar Iglesias, Marta Salido, Manuel Gallen, Scot Marsters, Siao Ping Tsai, André Minoche, Somasekar Seshagiri, Sergi Serrano, Heinz Himmelbauer, Joaquim Bellmunt, Ana Rovira, Jeff Settleman, Francesc Bosch, Joan Albanell, Identification of a mutation in the extracellular domain of the Epidermal Growth Factor Receptor conferring cetuximab resistance in colorectal cancer Nature Medicine. ,vol. 18, pp. 221- 223 ,(2012) , 10.1038/NM.2609

K. Yonesaka, K. Zejnullahu, I. Okamoto, T. Satoh, F. Cappuzzo, J. Souglakos, D. Ercan, A. Rogers, M. Roncalli, M. Takeda, Y. Fujisaka, J. Philips, T. Shimizu, O. Maenishi, Y. Cho, J. Sun, A. Destro, K. Taira, K. Takeda, T. Okabe, J. Swanson, H. Itoh, M. Takada, E. Lifshits, K. Okuno, J. A. Engelman, R. A. Shivdasani, K. Nishio, M. Fukuoka, M. Varella-Garcia, K. Nakagawa, P. A. Janne, Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab Science Translational Medicine. ,vol. 3, ,(2011) , 10.1126/SCITRANSLMED.3002442

Alberto Bardelli, Salvatore Siena, Molecular Mechanisms of Resistance to Cetuximab and Panitumumab in Colorectal Cancer Journal of Clinical Oncology. ,vol. 28, pp. 1254- 1261 ,(2010) , 10.1200/JCO.2009.24.6116

Rafael G. Amado, Michael Wolf, Marc Peeters, Eric Van Cutsem, Salvatore Siena, Daniel J. Freeman, Todd Juan, Robert Sikorski, Sid Suggs, Robert Radinsky, Scott D. Patterson, David D. Chang, Wild-TypeKRASIs Required for Panitumumab Efficacy in Patients With Metastatic Colorectal Cancer Journal of Clinical Oncology. ,vol. 26, pp. 1626- 1634 ,(2008) , 10.1200/JCO.2007.14.7116

Yang Lu, Xinqun Li, Ke Liang, Rodney Luwor, Zahid H. Siddik, Gordon B. Mills, John Mendelsohn, Zhen Fan, Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the Anti-EGFR monoclonal antibody cetuximab Cancer Research. ,vol. 67, pp. 8240- 8247 ,(2007) , 10.1158/0008-5472.CAN-07-0589

Jan B. Vermorken, Ricard Mesia, Fernando Rivera, Eva Remenar, Andrzej Kawecki, Sylvie Rottey, Jozsef Erfan, Dmytro Zabolotnyy, Heinz-Roland Kienzer, Didier Cupissol, Frederic Peyrade, Marco Benasso, Ihor Vynnychenko, Dominique De Raucourt, Carsten Bokemeyer, Armin Schueler, Nadia Amellal, Ricardo Hitt, Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer The New England Journal of Medicine. ,vol. 359, pp. 1116- 1127 ,(2008) , 10.1056/NEJMOA0802656

Derek J. Jonker, Chris J. O'Callaghan, Christos S. Karapetis, John R. Zalcberg, Dongsheng Tu, Heather-Jane Au, Scott R. Berry, Marianne Krahn, Timothy Price, R. John Simes, Niall C. Tebbutt, Guy van Hazel, Rafal Wierzbicki, Christiane Langer, Malcolm J. Moore, Cetuximab for the Treatment of Colorectal Cancer The New England Journal of Medicine. ,vol. 357, pp. 2040- 2048 ,(2007) , 10.1056/NEJMOA071834