Browse
Submit Data
Databases
API
Help

Dataset Information

3 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Biomarker Directed Treatment in Metastatic Colorectal Cancer

ABSTRACT: This pilot study is being mounted to assess whether treatment assignment by ERCC-1 gene expression status suggests better clinical results from historical experience in metastatic colorectal cancer (mCRC). In wild type KRAS mCRC patients treated with either FOLFOX or FOLFIRI in combination with cetuximab the median response rate is approximately 60-65%. Biomarker directed treatment in this study may demonstrate that patients with low ERCC-1 treated with FOLFOX and cetuximab, and those with high ERCC-1 treated with FOLFIRI and cetuximab, will improve response rate to 70-75%. KRAS wild type patients will be treated with 6 cycles of one of the following regimens chosen for optimization based on patient characteristics (primary treatment phase). Patients with ERCC-1 < 1.7 relative gene expression of ERCC-1 over ß-actin (ERCC-1 low) will be assigned to treatment with mFOLFOX6 in combination with Cetuximab. Patients with ERCC-1 gene expression > 1.7 relative gene expression of ERCC-1 over over ß-actin (ERCC-1 high) will be assigned to treatment with FOLFIRI in combination with Cetuximab.

DISEASE(S): Metastatic Colorectal Cancer,This Pilot Study Is Being Mounted To Assess Whether Treatment Assignment By Ercc-1 Gene Expression Status Suggests Better Clinical Results From Historical Experience In Mcrc.,Colorectal Cancer Metastatic,Colorectal Neoplasms

PROVIDER: 2133316 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

ACCESS DATA

Json Xml

Similar Datasets

Identification of SNP candidates associated with chemo-responsiveness in colorectal cancer patients

Project description:Response rates of 118 colorectal cancer patients to regiments were evaluated by histoculture drug response assay. Affymetrix SNP 6.0 chips were used to determine genotypes of the same colorectal cancer patients. SNPs associated with chemosensitivity to treatment regiments were identified by genome-wide association study. AV: avastin (Bevacizumab), ER: Erbitux (Cetuximab), FXA: bevacizumab + FOLFOX, FXE: Cetuximab + FOLFOX , FRA: Bevacizumab + FOLFIRI, FRE: Cetuximab + FOLFIRI; Numbers (0-100) represent responsiveness to the given drug regimens; the larger, the better responsive to given regimens

2011-03-25 | GSE21228 | GEO

Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models

Project description:Global mRNA expression profiling of patient derived colon cancer xenograft models (N=10) showing disease control under cetuximab treatment were collected using Agilent human whole genome array (G4845A AMADID 026652, cRNA 4x44k V2) . All xenograft models were wildtype for KRAS, NRAS, BRAF and PIK3CA. All Mice were treated with cetuximab (Merck Serono) by intra peritoneal (i.p.) injection twice per week and dosed at 25mg/kg to establish response characteristics. Tumors were chronically treated to establish cetuximab secondary resistant tumors .

2021-05-21 | GSE140973 | GEO

Global gene expression analysis between cetuximab-sensitive and cetuximab-resistant colorectal cancer cells

Project description:Cetuximab is an epidermal growth factor receptor (EGFR)-blocking antibody approved for treatment of metastatic colorectal cancer. We examined differences in global gene expression between the syngeneic DiFi colorectal cancer cells, and a subline of DiFi cells with acquired resistance to cetuximab (DiFi5). We used Affymetrix HG-U133A array to compare the expression pattern of genes that are up-regulated or down-regulated between the parental DiFi colorectal cancer cells and the cetuximab-resistant DiFi5 cells. We generated a cetuximab-resistant DiFi subline, termed DiFi5, by chronic exposure of parental DiFi cells to serially increased doses of cetuximab (from 0.5 nM to 5 nM) for over 1 year. The resulting DiFi5 subline exhibits significant resistance to cetuximab-induced apoptosis. After we confirmed that the phenotype was stable over a period of time of more than 6 months, the RNA from DiFi and DiFi5 cells were extracted and hybridized to an Affymetrix HG-U133A array according to the manufacturerâs instructions. Following the hybridization, the array was scanned using a laser confocal scanner, and microarray image data were analyzed using DNA-Chip Analyzer (dChip), version 1.3, by the Sequencing and Microarray Facility at MD Anderson Cancer Center.

2016-07-17 | E-GEOD-71210 | biostudies-arrayexpress

HesseMuellerRelogio2023 - Timing treatment toxicity of the cancer drug irinotecan based on circadian gene expression profiles

Project description:Chronotherapy demands that patients are treated at a particular time of the day in order to maximize treatment effects and minimize side effects. Chronotherapy can be personalized by taking into account the patient's circadian rhythm as measured by a repetitive sampling of gene expression over the day. As a proof of concept, the submitted model links circadian gene expression to the diurnal toxicity profile of the cancer drug irinotecan. The model is based on MODEL2109140001; it implements a transcription-translation network model of the core clock and additional genes associated with irinotecan metabolism and links this to a model of the pharmacokinetics and -dynamics (PK-PD) of irinotecan. The submitted model refines network connections of the gene regulatory network and adds a treatment-induced increase in UGT1A1 and a transient increase in the apoptosis rate in response to treatment for the PK-PD part.

2023-06-27 | MODEL2305270001 | BioModels

Secondary Resistance to Anti-EGFR Therapy by Transcriptional Reprogramming in Patient-Derived Colorectal Cancer Models

Project description:3' RNA-seq of patient derived colon cancer xenograft models (N=10) showing initial disease control under cetuximab treatment were collected. All xenograft models were wildtype for KRAS, NRAS, BRAF and PIK3CA. All mice were treated with cetuximab (Merck Serono) by intra peritoneal (i.p.) injection twice per week and dosed at 25mg/kg to establish response characteristics. Tumors were chronically treated to establish cetuximab secondary resistant tumors .

2021-06-14 | GSE141861 | GEO

The expression profile of Cetuximab resistance in head-and-neck squamous cell carcinoma cells.

Project description:Cetuximab (Erbitux) is an antibody drug against EGFR and commonly used in late stage HNSCC and metastatic colorectal cancer. The oncogenic mutation of certain genes are known to drive Cetuximab resistance such as K-RAS or b-RAF mutation. The aberrant activation of signaling pathways in the presence of Cetuximab treatment to overcome cellular stress contribute to acquired resistance to Cetuximab as well. To better understand the mechanisms and molecular patterns of Cetuximab resistant cells, the Cetuximab resistant cells are trained for examining the gene expression profile. The gene expression array is used for identify the molecular signature governing the Cetuximab resitance.

2017-03-02 | GSE63916 | GEO

Effects of EGF, cetuximab, trastuzumab and afatinib on gene expression in gastric cancer cell lines

Project description:The antibody trastuzumab in combination with platin-fluoropyrimidine chemotherapy is the standard of care for patients with HER2-positive recurrent or metastatic gastric cancer. Alternative treatment options and biomarkers for prediction of therapy response are needed since some patients do not respond to trastuzumab therapy or develop acquired resistance. We compared the molecular effects of trastuzumab and other HER-targeting drugs cetuximab and afatinib. We also tested the hypothesis that the treatment-dependent regulation of a gene indicates its importance for response, and therefore it may be used as biomarker for patient stratification. The four gastric cancer cell lines Hs746T, MKN1, MKN7 and NCI-N87 were treated with EGF, cetuximab, trastuzumab or afatinib for 4 or 24 hours. The effect on gene expression was then measured by RNA sequencing and the resulting candidate biomarkers were tested in an available cohort of gastric cancer patients or were functionally analyzed in vitro. Treatment with afatinib resulted in the highest number of regulated genes, followed by cetuximab and trastuzumab. Although trastuzumab had little effects on gene expression, we identified BMF, HAS2 and SHB as candidate biomarkers for trastuzumab response. HAS2 and SHB were confirmed as potential predictive markers for trastuzumab therapy response in clinical specimens. AREG, EREG and HBEGF were identified as candidate biomarkers for afatinib and cetuximab treatment. The functional analysis confirmed HBEGF as resistance factor for cetuximab. By confirming HAS2, SHB and HBEGF as biomarkers for anti-HER therapies, we provide evidence that the regulation of gene expression after treatment can be used for biomarker discovery.

2020-11-02 | GSE141352 | GEO

TGF-beta and BMP mediated gene expression in cultured sclerotome.

Project description:Very little is known about how intervertebral disc (IVD) is formed or maintained. Members of the TGF-ß superfamily are secreted signaling proteins that regulate many aspects of development including cellular differentiation. We recently showed that deletion of Tgfbr2 in Col2a expressing tissue results in alterations in development of IVD annulus fibrosus. The results suggested TGF-ß has an important role in regulating development of the axial skeleton, however, the mechanistic basis of TGF-ß action in these specialized joints is not known. To understand the mechanism of TGF-ß action in IVD development, we undertook a global analysis of gene expression comparing gene expression profiles in sclerotome cultures treated with TGF-ß or BMP4. As expected, treatment with BMP4 resulted in up-regulation of cartilage marker genes including Acan, Sox 5, Sox6, and Sox9. In contrast, treatment with TGF-ß1 did not regulate expression of cartilage markers but instead resulted in up-regulation of many IVD markers including Fmod and Adamtsl2. We propose TGF-ß has two functions in IVD development: 1) to prevent chondrocyte differentiation in the presumptive IVD and 2) to promote differentiation of annulus fibrosus from sclerotome. We have identified genes that are enriched in the IVD and regulated by TGF-ß that warrant further investigation as regulators of IVD development.

2010-04-09 | GSE18648 | GEO