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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Colorectal cancer classification based on gene expression is not associated with FOLFIRI response

ABSTRACT: Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: “A colorectal cancer classification system that associates cellular phenotype and responses to therapy”. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response. We used the classification algorithm to obtain CRC subtypes from our samples. Then we tested the subtype-drug response association performing a retrospective study.

ORGANISM(S): Homo sapiens

SUBMITTER: Manuel Hidalgo

PROVIDER: E-GEOD-54483 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Colorectal cancer classification based on gene expression is not associated with FOLFIRI response

Project description:Sadanandam et al. (2013) recently published a study based on the use of microarray data to classify colorectal cancer (CRC) samples. The classification claimed to have strong clinical implications, as reflected in the paper title: “A colorectal cancer classification system that associates cellular phenotype and responses to therapy”. They defined five subtypes: (i) inflammatory; (ii) goblet-like; (iii) enterocyte; (iv) transit-amplifying; and (v) stem-like. Based on drug sensitivity data from 21 patients, they also reported that the so-called stem-like subtype show differential sensitivity to FOLFIRI. This is the key result in their publication, since it implies a direct relation between the subtype and the choice of CRC therapy (i.e. FOLFIRI response). However, our analyses using the same drug sensitivity data and results from additional patients showed that the CRC classification reported by Sadanandam et al. is not predictive of FOLFIRI response.

2014-09-10 | GSE54483 | GEO

Consensus Molecular Subtype predicts differential vulnerability of colorectal cancer to the survivin suppressant YM155 II

Project description:Tumor heterogeneity is a major challenge to the treatment of colorectal cancer (CRC). Recently, a transcriptome-based classification was developed, segregating CRC into four consensus molecular subtypes (CMS) with distinct biological and clinical characteristics. Here, we applied the CMS classification on CRC cell lines to identify novel subtype-specific drug vulnerabilities. We combined publicly available transcriptome data from multiple resources to assign 159 CRC cell lines to CMS. By integrating results from large scale drug screens, we discovered that CMS1 cancer is highly vulnerable to the survivin suppressor YM155. We confirmed our results using an independent panel of CRC cell lines and demonstrate a 100-fold higher sensitivity of CMS1 lines. This vulnerability was specific to YM155 and not observed for commonly used chemotherapeutic agents. In CMS1 cancer, low concentrations of YM155 induced apoptosis and expression signatures associated with NFkappaB and ER stress mediated apoptosis signaling. Using a genome-wide CRISPR/Cas9 screen, we discovered a novel role of genes involved in LDL-receptor recycling as modulators of YM155 response in CMS1 CRC. Our work shows that combining drug response data with CMS classification in cell lines can reveal specific vulnerabilities and propose YM155 as novel CMS1 specific drug. We performed expression profiling experiments in order to validate molecular subtypes for selected cell lines

2018-07-03 | GSE116528 | GEO

Consensus Molecular Subtype predicts differential vulnerability of colorectal cancer to the survivin suppressant YM155 I

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Molecular subtypes of metastatic colorectal cancer are predictive of patient response to chemo and targeted therapies (part 1)

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AKT dependent Notch3 activation drives tumor progression in a model of mesenchymal colorectal cancer subtype

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