Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma

Chong Sun, Liqin Wang, Sidong Huang, Guus J. J. E. Heynen, Anirudh Prahallad, Caroline Robert, John Haanen, Christian Blank, Jelle Wesseling, Stefan M. Willems, Davide Zecchin, Sebastijan Hobor, Prashanth K. Bajpe, Cor Lieftink, Christina Mateus, Stephan Vagner, Wipawadee Grernrum, Ingrid Hofland, Andreas Schlicker, Lodewyk F. A. Wessels, Roderick L. Beijersbergen, Alberto Bardelli, Federica Di Nicolantonio, Alexander M. M. Eggermont and Rene Bernards ()
Additional contact information
Chong Sun: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Liqin Wang: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Sidong Huang: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Guus J. J. E. Heynen: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Anirudh Prahallad: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Caroline Robert: Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France
John Haanen: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Christian Blank: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Jelle Wesseling: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Stefan M. Willems: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Davide Zecchin: University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
Sebastijan Hobor: Candiolo Cancer Institute – FPO, IRCCS, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
Prashanth K. Bajpe: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Cor Lieftink: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Christina Mateus: Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France
Stephan Vagner: Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France
Wipawadee Grernrum: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Ingrid Hofland: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Andreas Schlicker: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Lodewyk F. A. Wessels: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Roderick L. Beijersbergen: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
Alberto Bardelli: University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
Federica Di Nicolantonio: University of Torino, Str prov 142 Km 3.95, 10060 Candiolo, Torino, Italy
Alexander M. M. Eggermont: Institut Gustave Roussy, 114 Rue Edouard Vaillant, 94800 Villejuif, France
Rene Bernards: Cancer Systems Biology Centre and Cancer Genomics Centre Netherlands, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

Nature, 2014, vol. 508, issue 7494, 118-122

Abstract: Patients with melanomas carrying an activating BRAF mutation respond to treatment with BRAF inhibitors although resistance to the inhibitor usually emerges; this resistance is shown to arise through increased expression of receptor tyrosine kinases such as EGFR; however, these changes decrease cell fitness and during a break from inhibitor treatment these cells are selected against, revealing that some patients who acquire EGFR expression may benefit from inhibitor re-treatment after a drug holiday.

Date: 2014
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DOI: 10.1038/nature13121

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