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

来自 Semantic Scholar

阅读量：

337

摘要：

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.

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关键词：

Humans Colon Colorectal Neoplasms Neoplasm Metastasis Antineoplastic Agents Treatment Outcome Oligonucleotide Array Sequence Analysis Genetic Markers Gene Expression Profiling Signal Transduction

DOI：

10.1038/nm.3175

被引量：

765

年份：

2013

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来源期刊

Nature Medicine
2013 May;

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2015
被引量：220

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