Lack of Benefit of 5-Fluorouracil-Based Adjuvant Chemotherapy in Colorectal Cancer with Microsatellite Instability

Johnson, Lori; Chu, Edward

doi:10.1016/s1533-0028(11)70320-6

Cited by 6 publications

(3 citation statements)

References 8 publications

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“…However, an overall reduced benefit from adjuvant therapy in patients with MSI and CRC could not be demonstrated in a meta-analysis [36] , but the overall survival of MSI cancers was better. Again, results evolved over the past few years have shown equivocal results concerning both survival and chemotherapy response [38-42, 47, 48] , thus further blurring the true prognostic and predictive value of MSI in sporadic CRC [49,50] . However, in vitro studies have shown that MSI-H colon cancer cell lines are more resistant to 5-FU compared to MSS cell lines.…”

Section: Predictive Value Of Msimentioning

confidence: 99%

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Søreide

2007

Tumor Biol

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Microsatellite instability (MSI) is a genetic feature of colorectal cancer (CRC) associated with peculiar clinicopathological features and improved prognosis. It is demonstrated in >90% of patients with hereditary non-polyposis colorectal cancer (HNPCC) in which DNA mismatch repair (MMR) defects are the cause of MSI. HNPCC develop at a young age, and patients are at increased risk for additional cancers (e.g. endometrial, stomach, or biliary tract cancer). MSI is found in 15–20% of sporadic CRC, often based on epigenetic silencing (i.e. MLH1). The prognostic and predictive value of MSI is not yet fully elucidated, although improved survival in MSI is suggested. Distinguishing sporadic MSI from HNPCC is at present guided by the combination of familial history, immunohistochemistry, and genotyping of MMR genes (MLH1, MSH2, MSH6, and PMS2). The efficiency and accuracy of MSI testing is evolving, with more knowledge achieved concerning multipopulation polymorphisms, selection of markers (e.g. quasimonomorphic vs. dinucleotides), and more time-efficient panels (e.g. not requiring normal/germline DNA match). The role of distinct genetic features, such as BRAF V600E mutations often found in sporadic MSI but not in HNPCC, may further improve future test algorithms. The present knowledge and controversies pertaining to molecular testing of MSI and MMR defects in CRC are presented.

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Section: Predictive Value Of Msimentioning

confidence: 99%

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Søreide

2007

Tumor Biol

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“…In reviewing this subject, Lynch et al suggest that" The issue of survival will confound studies that are not prospectively randomized and stratified for MSI status. Nonetheless, a failure to demonstrate survival benefits after adjuvant chemotherapy in patients with MSI + tumors or with Lynch syndrome has been demonstrated by most subsequent investigators [25][26][27][28]" [23].…”

Section: R Re Ef Fe Er Re En Nc Ce Es Smentioning

confidence: 99%

Discussion on the use of taxanes for treatment of breast cancers in BRCA1 mutations carriers

Elsakov

Foretová

Goetz

et al. 2007

Hered Cancer Clin Pract

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“…Since methotrexate efflux was increased sponse. [70] after treatment with decitabine Worm et al [10] assumed that decitabine upregulates both methotrexate uptake and some metho-…”

Section: Hypermethylation Of Dna Repair Genes Andmentioning

confidence: 99%

Identifying DNA Methylation Biomarkers of Cancer Drug Response

Maier

Dahlstroem

Haefliger

et al. 2005

American Journal of PharmacoGenomics

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In the last few years, DNA methylation has become one of the most studied gene regulation mechanisms in carcinogenesis as a result of the cumulative evidence produced by the scientific community. Moreover, advances in the technologies that allow detection of DNA methylation in a variety of analytes have opened the possibility of developing methylation-based tests. A number of studies have provided evidence that specific methylation changes can alter the response to different therapeutic agents in cancer and, therefore, be useful biomarkers. For example, the association of the methylation status of DNA repair genes such as MGMT and MLH1 illustrate the two main mechanisms of response to DNA damaging agents. Loss of methylation of MGMT, and the subsequent increase in gene expression, leads to a reduction in response to alkylating agents as a result of enhanced repair of drug-induced DNA damage. Conversely, the increase in methylation of MLH1 and its resulting loss of expression has been consistently observed in drug-resistant tumor cells. MLH1 encodes a mismatch repair enzyme activated in response to DNA damage; activation of MLH1 also induces apoptosis of tumor cells, and thus loss of its expression leads to resistance to DNA-damaging agents. Other methylation-regulated genes that could serve as biomarkers in cancer therapy include drug transporters, genes involved in microtubule formation and stability, and genes related to hormonal therapy response. These methylation markers have potential applications for disease prognosis, treatment response prediction, and the development of novel treatment strategies.

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Lack of Benefit of 5-Fluorouracil-Based Adjuvant Chemotherapy in Colorectal Cancer with Microsatellite Instability

Cited by 6 publications

References 8 publications

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Discussion on the use of taxanes for treatment of breast cancers in BRCA1 mutations carriers

Identifying DNA Methylation Biomarkers of Cancer Drug Response

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Lack of Benefit of 5-Fluorouracil-Based Adjuvant Chemotherapy in Colorectal Cancer with Microsatellite Instability

Cited by 6 publications

References 8 publications

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers &ndash; Ready for Prime Time?

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers &ndash; Ready for Prime Time?

Discussion on the use of taxanes for treatment of breast cancers in BRCA1 mutations carriers

Identifying DNA Methylation Biomarkers of Cancer Drug Response

Contact Info

Product

Resources

About

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?

Molecular Testing for Microsatellite Instability and DNA Mismatch Repair Defects in Hereditary and Sporadic Colorectal Cancers – Ready for Prime Time?