Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion

Ravid Straussman, Teppei Morikawa, Kevin Shee, Michal Barzily-Rokni, Zhi Rong Qian, Jinyan Du, Ashli Davis, Margaret M. Mongare, Joshua Gould, Dennie T. Frederick, Zachary A. Cooper, Paul B. Chapman, David B. Solit, Antoni Ribas, Roger S. Lo, Keith T. Flaherty, Shuji Ogino, Jennifer A. Wargo and Todd R. Golub ()
Additional contact information
Ravid Straussman: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Teppei Morikawa: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA
Kevin Shee: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Michal Barzily-Rokni: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Zhi Rong Qian: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA
Jinyan Du: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Ashli Davis: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Margaret M. Mongare: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Joshua Gould: The Eli and Edythe L. Broad Institute, 7 Cambridge Center
Dennie T. Frederick: Medical Oncology and Dermatology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
Zachary A. Cooper: Medical Oncology and Dermatology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
Paul B. Chapman: Memorial Sloan-Kettering Cancer Center
David B. Solit: Memorial Sloan-Kettering Cancer Center
Antoni Ribas: Jonsson Comprehensive Cancer Center, University of California
Roger S. Lo: Jonsson Comprehensive Cancer Center, University of California
Keith T. Flaherty: Medical Oncology and Dermatology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
Shuji Ogino: Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02115, USA
Jennifer A. Wargo: Medical Oncology and Dermatology, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA
Todd R. Golub: The Eli and Edythe L. Broad Institute, 7 Cambridge Center

Nature, 2012, vol. 487, issue 7408, 500-504

Abstract: The secretion of hepatocyte growth factor by stromal cells in the tumour micro-environment can make melanoma resistant to RAF inhibitors, through the activation of the MET signalling pathway, but a combination of RAF and MET inhibitors can overcome this resistance.

Date: 2012
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DOI: 10.1038/nature11183

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