Oncogenic pathway signatures in human cancers as a guide to targeted therapies

Andrea H. Bild, Guang Yao, Jeffrey T. Chang, Quanli Wang, Anil Potti, Dawn Chasse, Mary-Beth Joshi, David Harpole, Johnathan M. Lancaster, Andrew Berchuck, John A. Olson, Jeffrey R. Marks, Holly K. Dressman, Mike West and Joseph R. Nevins ()
Additional contact information
Andrea H. Bild: Duke University
Guang Yao: Duke University
Jeffrey T. Chang: Duke University
Quanli Wang: Duke University
Anil Potti: Duke University
Dawn Chasse: Duke University
Mary-Beth Joshi: Department of Surgery
David Harpole: Department of Surgery
Johnathan M. Lancaster: University of South Florida
Andrew Berchuck: Duke University Medical Center
John A. Olson: Duke University
Jeffrey R. Marks: Department of Surgery
Holly K. Dressman: Duke University
Mike West: Duke University
Joseph R. Nevins: Duke University

Nature, 2006, vol. 439, issue 7074, 353-357

Abstract: Tumour profiling advances Molecular tumour profiling is one way in which effective targeted cancer treatment regimes might be developed. Two groups report significant developments in this direction. Bild et al. studied gene expression patterns that reflect the activation of various oncogenic (cancer-causing) signal transduction pathways. Using combinations of these pathway signatures, they predict which patients with breast, lung or ovarian cancer have a particularly poor prognosis. The ability to identify molecular pathways that are deregulated in a particular cancer in this way might be used to predict its sensitivity to specific therapeutic drugs. Solit et al. studied tumour cells with mutations in the RAS and BRAF genes, thought to cause cancer at least in part by activating the MEK/ERK signalling pathway. They show that tumours with the BRAF mutation, but not RAS, are highly sensitive to PD0325901, an MEK inhibitor that is in early-stage clinical trials in patients with melanoma, colon, breast and lung cancers. So by testing for the presence of BRAF mutations it may be possible to identify those patients most likely to benefit from this type of drug.

Date: 2006
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DOI: 10.1038/nature04296

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