ArticleBritish journal of cancer2008
Microsatellite instability due to hMLH1 deficiency is associated with increased cytotoxicity to irinotecan in human colorectal cancer cell lines.
Article in British journal of cancer, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 85 citations in OpenAlex.
- Trial
- Predictive and prognostic roles of BRAF mutation in stage III colon cancer: results from intergroup trial CALGB 89803.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Trial
- CRISPR Screening Identifies SMARCAL1 and MRN as Modulators of WRN Dependency in MSI-H Colorectal Cancer.Cancer research · 2026Article
- Predicting therapeutic responses in metastatic colorectal cancer through personalized functional profiling of patient-derived spheroids.NPJ precision oncology · 2026Article
- Mechanism of DNA unwinding by hexameric MCM8-9 in complex with HROB.Research square · 2023Article
- Evolution of Resistance to Irinotecan in Cancer Cells Involves Generation of Topoisomerase-Guided Mutations in Non-Coding Genome That Reduce the Chances of DNA Breaks.International journal of molecular sciences · 2023Article
- Resistance to TOP-1 Inhibitors: Good Old Drugs Still Can Surprise Us.International journal of molecular sciences · 2023Review
- Design, synthesis, and biological evaluation of tetrahydroquinolinones and tetrahydroquinolines with anticancer activity.Scientific reports · 2022Article
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- Genomic Alterations and Their Implications on Survival in Nonmetastatic Colorectal Cancer: Status Quo and Future Perspectives.Cancers · 2020Review
- MRN (MRE11-RAD50-NBS1) Complex in Human Cancer and Prognostic Implications in Colorectal Cancer.International journal of molecular sciences · 2019Review
- Phase IB Study of Vemurafenib in Combination with Irinotecan and Cetuximab in Patients with Metastatic Colorectal Cancer with BRAFV600E Mutation.Cancer discovery · 2016Article
- Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism.Oncotarget · 2016Article
- Integrative Omics Analysis Reveals Post-Transcriptionally Enhanced Protective Host Response in Colorectal Cancers with Microsatellite Instability.Journal of proteome research · 2016Article
- Implications of mismatch repair-deficient status on management of early stage colorectal cancer.Journal of gastrointestinal oncology · 2015Review
- Association between mismatch repair gene and irinotecan-based chemotherapy in metastatic colon cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Review
- Overexpression of KDM4 lysine demethylases disrupts the integrity of the DNA mismatch repair pathway.Biology open · 2015Article
- DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers.Journal of gynecologic oncology · 2015Article
- Treatment with the PARP inhibitor, niraparib, sensitizes colorectal cancer cell lines to irinotecan regardless of MSI/MSS status.Cancer cell international · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Around 15% of colorectal cancers (CRCs) show microsatellite instability (MSI) due to dysfunction of the mismatch repair system (MMR). As a consequence of this, MSI tumours tend to accumulate errors in mononucleotide repeats as those in genes implicated in repairing double-strand breaks (DSBs). Previous studies have shown that irinotecan (CPT-11), a chemotherapy agent inducing DSB, is more active in MSI than in microsatellite stable (MSS) CRC. The purpose of this study was to compare the sensitivity to CPT-11 in a series of CRC cell lines with either proficient or deficient MMR and to assess the mutational status of two DSB repair genes, MRE11 and RAD50, in these cell lines. hMLH1-deficient cell lines due to either epigenetic silencing or mutation showed very similar IC(50) and were four- to nine-fold more sensitive to CPT-11 than the MSS line. Cell lines harbouring mutations in both MRE11 and RAD50 were most sensitive to CPT-11. We conclude that MSI cell lines display higher sensitivity to CPT-11 than MSS cells. Mutation of MRE11 and RAD50 could account for this difference in response to CPT-11. Future clinical trials tailoring chemotherapy regimens based on microsatellite status are warranted.
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