ArticleCancer research2011
MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers.
Article in Cancer research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 2 of them syntheses that pooled it.
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Who cites it
102 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Continuity of transcriptomes among colorectal cancer subtypes based on meta-analysis.Genome biology · 2018Pooled it
- Meta-analysis of organ-specific differences in the structure of the immune infiltrate in major malignancies.Oncotarget · 2015Pooled it
- Phase II Study of Olaparib (AZD-2281) After Standard Systemic Therapies for Disseminated Colorectal Cancer.The oncologist · 2016Trial
- Endothelial PARP1 orchestrates endothelial-to-mesenchymal transition via the PARylation of FHL2 in ischaemic heart failure.Acta pharmacologica Sinica · 2026Article
- Sensitizing Colorectal Cancer to PARP Inhibitors: Biomarkers, Mechanisms, and Combination Strategies.International journal of molecular sciences · 2026Review
- PARP Inhibitor Sensitivity in Tumors Harboring Non-BRCA Homologous Recombination Gene Alterations: Current Evidence Across Ovarian, Breast, Prostate, and Pancreatic Cancers.International journal of molecular sciences · 2026Review
- MRE11 Deficiency Occurs in a Small Group of Cancers from Various Different Tumor Entities.Diagnostics (Basel, Switzerland) · 2026Article
- Sex Differences in Colorectal Tumor-Associated T-cell Responses.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2026Article
- Rs12516 A allele elevates the risk of colorectal cancer via functional CeRNA network of BDNF-AS, miR-4704-5p and BRCA1.BMC cancer · 2026Article
- Targeting PARP-1 and DNA Damage Response Defects in Colorectal Cancer Chemotherapy with Established and Novel PARP Inhibitors.Cancers · 2024Article
- The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors.NPJ precision oncology · 2024Review
- Identification of 8 candidate microsatellite instability loci in colorectal cancer and validation of the ACVR2A mechanism in the tumor progression.Scientific reports · 2024Article
- Microsatellite instability states serve as predictive biomarkers for tumors chemotherapy sensitivity.iScience · 2023Article
- Review
- Multi-omic analysis in normal colon organoids highlights MSH4 as a novel marker of defective mismatch repair in Lynch syndrome and microsatellite instability.Cancer medicine · 2023Article
- Article
- New perspectives on epigenetic modifications and PARP inhibitor resistance in HR-deficient cancers.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Targeting Mre11 overcomes platinum resistance and induces synthetic lethality in XRCC1 deficient epithelial ovarian cancers.NPJ precision oncology · 2022Article
- Spectrum of DNA mismatch repair failures viewed through the lens of cancer genomics and implications for therapy.Clinical science (London, England : 1979) · 2022Article
- Functional roles of ADP-ribosylation writers, readers and erasers.Frontiers in cell and developmental biology · 2022Review
42 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Microsatellite instability (MSI) is displayed by approximately 15% of colorectal cancers (CRC). Defective DNA mismatch repair generates mutations at repetitive DNA sequences such as those located in the double strand break (DSB) repair gene MRE11. We assessed the mutational status of MRE11 in a panel of 17 CRC cell lines and 46 primary tumors and found a strong correlation with MSI status in both cell lines and tumors. Therefore, we hypothesized that deficiency in MRE11 may sensitize CRC cells to poly(ADP-ribose) polymerase (PARP-1) inhibition based on the concept of synthetic lethality. We further assessed the activity of the PARP-1 inhibitor, ABT-888, in CRC cell lines and observed preferential cytotoxicity in those MSI cell lines harboring mutations in MRE11 compared with both wild-type cell lines and microsatellite stable (MSS) cell lines. A significant correlation between MRE11 expression levels and cytotoxicity to ABT-888 at 10 μM was observed (R² = 0.915, P < 0.001). Using two experimental approaches, including short hairpin RNA knocking down MRE11 in the wild-type and MSS cell line SW-480 and a second cell line model transfected with mutant MRE11, we experimentally tried to confirm the role of MRE11 in conferring sensitivity to PARP-1 inhibition. Both models led to changes in proliferation in response to ABT-888 at different concentrations, and a drug-response effect was not observed, suggesting a possible contribution of additional genes. We conclude that MSI colorectal tumors deficient in DSB repair secondary to mutation in MRE11 show a higher sensitivity to PARP-1 inhibition. Further clinical investigation of PARP-1 inhibitors is warranted in MSI CRCs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.