A Gene Expression Signature for Chemoradiosensitivity of Colorectal Cancer Cells

Spitzner, Melanie; Emons, Georg; Krämer, Frank; Gaedcke, Jochen; Rave-Fränk, Margret; Scharf, Jens‐Gerd; Burfeind, Peter; Becker, Heinz; Beißbarth, Tim; Ghadimi, B. Michael; Ried, Thomas; Grade, Marian

doi:10.1016/j.ijrobp.2010.06.023

Cited by 66 publications

(65 citation statements)

References 41 publications

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“…This particular histone demethylase secures a metastable chromatin state which contributes towards the ability of cells to tolerate drug exposure. Additionally, this chromatin state is dependent on IGF-1R signaling, which has also been associated with drug resistance in a number of other studies [124,125].…”

Section: Pharmacoepigenomicsmentioning

confidence: 98%

Acquired and Intrinsic Resistance to Colorectal Cancer Treatment

Briffa¹,

Langdon²,

Grech³

et al. 2018

Colorectal Cancer - Diagnosis, Screening and Management

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First line therapy for colorectal cancer (CRC) is usually fluoropyrimidine monotherapy and oxaliplatin, or irinotecan-based therapy. Additionally, targeted therapies such as bevacizumab, aflibercept, ramucirumab, regorafenib, cetuximab and panitumumab are indicated in combination with chemotherapy in metastatic CRC. Resistance of CRC to treatment is the principal rationale for treatment failure. Resistance can be intrinsic (primary resistance) or acquired (secondary resistance). Here, we discuss the classical model of resistance, which focuses primarily on mechanisms involving alterations in drug metabolism, increased drug efflux, secondary mutations in drug targets, inactivation of apoptotic pathways, p53 and DNA damage repair. Other resistance mechanisms, including the Warburg effect, cancer stem cells, intra-tumor heterogeneity and pharmacoepigenomic mechanisms will also be discussed. We conclude the chapter with a systems medicine approach to predict response to treatment for the discovery and validation of predictive biomarkers that are urgently needed.

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Section: Pharmacoepigenomicsmentioning

confidence: 98%

Acquired and Intrinsic Resistance to Colorectal Cancer Treatment

Briffa¹,

Langdon²,

Grech³

et al. 2018

Colorectal Cancer - Diagnosis, Screening and Management

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“…Similarly another study identified a gene expression signature of 42 genes that was able to distinguish responder from non responder locally advanced RC patients with a 71% accuracy [192]. Recently; Spitzner et al were able to identify a gene expression signature for chemoradiosensitivity of colorectal cancer cells [193].…”

Section: Therapeutic Targets and Treatment Response Predictionmentioning

confidence: 99%

“…Some studies evaluated the ability of gene expression profiling for predicting response of advanced rectal cancer (RC) to preoperative chemoradiotherapy [186,[191][192][193]. Ghadimi [191].…”

Section: Therapeutic Targets and Treatment Response Predictionmentioning

confidence: 99%

784 Clinical applications of molecular profiling of colorectal cancer

Kheirelseid¹,

Miller²,

Chang³

et al. 2010

European Journal of Cancer Supplements

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“…Furthermore, it has been reported that peripheral blood lymphocyte subsets were associated with susceptibility to preoperative CRT (16). Additionally, the genes signal transducer and activator of transcription 3, Ras association (RalGDS̸AF-6) domain family member 1, docking protein 3 and erbB-2 receptor tyrosine kinase 2, were found to be associated with response to CRT in vitro (17). However, none of these factors have reached the stage where they may be clinically applied.…”

Section: Introductionmentioning

confidence: 99%

An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis

Empuku

Akagi

Kaneko

et al. 2016

Molecular and Clinical Oncology

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Abstract. Preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer not only improves the postoperative local control rate, but also induces downstaging. However, it has not been established how to individually select patients who receive effective preoperative CRT. The aim of this study was to identify a predictor of response to preoperative CRT for locally advanced rectal cancer. This study is additional to our multicenter phase II study evaluating the safety and efficacy of preoperative CRT using oral fluorouracil (UMIN ID: 03396). From April, 2009 to August, 2011, 26 biopsy specimens obtained prior to CRT were analyzed by cyclopedic microarray analysis. Response to CRT was evaluated according to a histological grading system using surgically resected specimens. To decide on the number of genes for dividing into responder and non-responder groups, we statistically analyzed the data using a dimension reduction method, a principle component analysis. Of the 26 cases, 11 were responders and 15 non-responders. No significant difference was found in clinical background data between the two groups. We determined that the optimal number of genes for the prediction of response was 80 of 40,000 and the functions of these genes were analyzed. When comparing non-responders with responders, genes expressed at a high level functioned in alternative splicing, whereas those expressed at a low level functioned in the septin complex. Thus, an 80-gene expression set that predicts response to preoperative CRT for locally advanced rectal cancer was identified using a novel statistical method.

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A Gene Expression Signature for Chemoradiosensitivity of Colorectal Cancer Cells

Cited by 66 publications

References 41 publications

Acquired and Intrinsic Resistance to Colorectal Cancer Treatment

Acquired and Intrinsic Resistance to Colorectal Cancer Treatment

784 Clinical applications of molecular profiling of colorectal cancer

An 80-gene set to predict response to preoperative chemoradiotherapy for rectal cancer by principle component analysis

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