A colorectal cancer classification system that associates cellular phenotype and responses to therapy.

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Serval ID
serval:BIB_A29B5E2F4014
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
A colorectal cancer classification system that associates cellular phenotype and responses to therapy.
Journal
Nature Medicine
Author(s)
Sadanandam A., Lyssiotis C.A., Homicsko K., Collisson E.A., Gibb W.J., Wullschleger S., Ostos L.C., Lannon W.A., Grotzinger C., Del Rio M., Lhermitte B., Olshen A.B., Wiedenmann B., Cantley L.C., Gray J.W., Hanahan D.
ISSN
1546-170X (Electronic)
ISSN-L
1078-8956
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
19
Number
5
Pages
619-625
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Colorectal cancer (CRC) is a major cause of cancer mortality. Whereas some patients respond well to therapy, others do not, and thus more precise, individualized treatment strategies are needed. To that end, we analyzed gene expression profiles from 1,290 CRC tumors using consensus-based unsupervised clustering. The resultant clusters were then associated with therapeutic response data to the epidermal growth factor receptor-targeted drug cetuximab in 80 patients. The results of these studies define six clinically relevant CRC subtypes. Each subtype shares similarities to distinct cell types within the normal colon crypt and shows differing degrees of 'stemness' and Wnt signaling. Subtype-specific gene signatures are proposed to identify these subtypes. Three subtypes have markedly better disease-free survival (DFS) after surgical resection, suggesting these patients might be spared from the adverse effects of chemotherapy when they have localized disease. One of these three subtypes, identified by filamin A expression, does not respond to cetuximab but may respond to cMET receptor tyrosine kinase inhibitors in the metastatic setting. Two other subtypes, with poor and intermediate DFS, associate with improved response to the chemotherapy regimen FOLFIRI in adjuvant or metastatic settings. Development of clinically deployable assays for these subtypes and of subtype-specific therapies may contribute to more effective management of this challenging disease.
Pubmed
Web of science
Create date
06/06/2013 18:06
Last modification date
20/08/2019 15:08
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