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

Sadanandam, Anguraj; Gray, Joe W.; Hanahan, Douglas

doi:10.1038/nm.3742

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…With regard to the prognostic significance of CIMP in CRC, overall negative associations between the CIMP status and clinical outcomes have been reported in studies including patients with early and locally advanced disease ( Van Rijnsoever et al , 2003 ; Shen et al , 2007 ; Ogino et al , 2007b ; Iacopetta et al , 2008 ; Kim et al , 2009 , 2011 ; Bae et al , 2011 , 2013 ; Jover et al , 2011 ; Min et al , 2011 ; Sadanandam et al , 2013 , 2014 ; Kim and Kang, 2014 ; Martinez-Garcia et al , 2014 ; Shiovitz et al , 2014 ; Sistigu et al , 2014 ). A recent meta-analysis of 19 studies also showed that the CIMP status is independently associated with significantly decreased disease-free survival and overall survival (OS) in patients with CRC ( Juo et al , 2014 ).…”

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confidence: 99%

Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer

et al. 2016

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Background:The association between the CpG island methylator phenotype (CIMP) and clinical outcomes in metastatic colorectal cancer remains unclear. We investigated the prognostic impact of CIMP in patients with metastatic colorectal cancer treated with systemic chemotherapy.Methods:Eight CIMP-specific promoters (CACNA1G, IGF2, NEUROG1, RUNX3, SOCS1, CDKN2A, CRABP1, and MLH1) were examined. The CIMP status was determined by the number of methylated promoters as high (⩾5), low (1–4), and negative (0).Results:A total of 153 patients were included (men/women, 103/50; median age, 61 years; range, 22–80 years). The CIMP status was negative/low/high in 77/ 69/7 patients, respectively. Overall survival (OS) was significantly different among the three CIMP groups, with median values of 35.7, 22.2, and 9.77 months for the negative, low, and high groups, respectively (P<0.001). For patients treated with fluoropyrimidine and oxaliplatin first-line chemotherapy (N=128), OS and progression-free survival (PFS) were significantly different among the three CIMP groups; the median OS was 37.9, 23.8, and 6.77 months for the negative, low, and high groups, respectively (P<0.001), while the median PFS was 9.97, 7.87, and 1.83 months, respectively (P=0.002). Response rates were marginally different among the three CIMP groups (53.4% vs 45.1% vs 16.7%, respectively; P=0.107). For patients treated with fluoropyrimidine and irinotecan second-line chemotherapy (N=86), only OS showed a difference according to the CIMP status, with median values of 20.4, 13.4, and 2.90 months for the negative, low, and high groups, respectively (P<0.001).Conclusions:The CIMP status is a negative prognostic factor for patients with metastatic colorectal cancer treated with chemotherapy.

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confidence: 99%

Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer

et al. 2016

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“…At metastatic disease these tumours appeared more sensitive to FOLFIRI, in which oxaliplatin is replaced for irinotecan 67 . Although available sample sizes of patients were initially too small to fully support the potential of irinotecan use 143 , 144 , two independent clinical trials with larger patient cohorts have since substantiated the enhanced effect of FOLFIRI over FOLFOX in CMS4 in the metastatic setting 133 , 145 .…”

Section: Translation Of Cms To the Clinicmentioning

confidence: 99%

Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges

2020

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Colon cancer inter-tumour heterogeneity is installed on multiple levels, ranging from (epi)genetic driver events to signalling pathway rewiring reflected by differential gene expression patterns. Although the existence of heterogeneity in colon cancer has been recognised for a longer period of time, it is sparingly incorporated as a determining factor in current clinical practice. Here we describe how unsupervised gene expression-based classification efforts, amongst which the consensus molecular subtypes (CMS), can stratify patients in biological subgroups associated with distinct disease outcome and responses to therapy. We will discuss what is needed to extend these subtyping efforts to the clinic and we will argue that preclinical models recapitulate CMS subtypes and can be of vital use to increase our understanding of treatment response and resistance and to discover novel targets for therapy.

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“…11 To resolve the inconsistencies among the reported gene expression-based classifications and to correlate CRC phenotype with clinical behavior, the CRC Subtyping Consortium unified six independent molecular classification systems and introduced a single consensus system known as the Consensus Molecular Subtypes (CMS). 12 CMS has four distinct groups that enable the categorization of most tumors into one of four subtypes (Table 1). [13][14][15] Even though CMS represents the current best description of heterogeneity at the gene-expression level, it also correlates the epigenomic, transcriptomic, microenvironmental, genetic, prognostic, and clinical characteristics of CRC (Table 1).…”

Section: Introductionmentioning

confidence: 99%

Understanding cell‐cell communication and signaling in the colorectal cancer microenvironment

AlMusawi

Ahmed

Nateri

2021

Clinical & Translational Med

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Carcinomas are complex heterocellular systems containing epithelial cancer cells, stromal fibroblasts, and multiple immune cell‐types. Cell‐cell communication between these tumor microenvironments (TME) and cells drives cancer progression and influences response to existing therapies. In order to provide better treatments for patients, we must understand how various cell‐types collaborate within the TME to drive cancer and consider the multiple signals present between and within different cancer types. To investigate how tissues function, we need a model to measure both how signals are transferred between cells and how that information is processed within cells. The interplay of collaboration between different cell‐types requires cell‐cell communication. This article aims to review the current in vitro and in vivo mono‐cellular and multi‐cellular cultures models of colorectal cancer (CRC), and to explore how they can be used for single‐cell multi‐omics approaches for isolating multiple types of molecules from a single‐cell required for cell‐cell communication to distinguish cancer cells from normal cells. Integrating the existing single‐cell signaling measurements and models, and through understanding the cell identity and how different cell types communicate, will help predict drug sensitivities in tumor cells and between‐ and within‐patients responses.

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

Cited by 5 publications

References 8 publications

Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer

Adverse prognostic impact of the CpG island methylator phenotype in metastatic colorectal cancer

Exploring and modelling colon cancer inter-tumour heterogeneity: opportunities and challenges

Understanding cell‐cell communication and signaling in the colorectal cancer microenvironment

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