ArticleCancer cell2010
DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1.
Article in Cancer cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 203 citations in OpenAlex.
- Rethinking ovarian cancer: recommendations for improving outcomes.Nature reviews. Cancer · 2011Guideline
- Replication Stress Tolerance in Adult T-Cell Leukemia.Biomolecules · 2026Review
- DNA Damage Recognition by Bacterial and Human Adenine-DNA Glycosylases: Insights from Non-Canonical Substrates.Biomolecules · 2026Article
- Inhibition of TGM2 enhances cisplatin sensitivity in MSH2-deficient bladder cancer.Cell death discovery · 2026Article
- Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.Cell proliferation · 2025Article
- Oxidative stress accelerates repeat sequence instability and base substitutions promoting gastrointestinal driver mutations in MSH2 deficient mice.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2025Article
- Mismatch Repair Deficiency and the Role of Non-Canonical Functions in Cancer: Diagnosis and Therapeutic Implications.International journal of molecular sciences · 2025Review
- Article
- Mitochondrial defects and metabolic vulnerabilities in Lynch syndrome-associated MSH2-deficient endometrial cancer.JCI insight · 2025Article
- Nonrepair functions of DNA mismatch repair proteins: new avenues for precision oncology.Trends in cancer · 2025Review
- DNA abasic sites act as rational therapeutic targets to synergize temozolomide response in both MMR-proficient and deficient cancer.NAR cancer · 2024Review
- AMPK Deficiency Increases DNA Methylation and Aggravates Colorectal Tumorigenesis in AOM/DSS Mice.Genes · 2024Article
- CDK-independent role of D-type cyclins in regulating DNA mismatch repair.Molecular cell · 2024Article
- D-type cyclins regulate DNA mismatch repair in the G1 and S phases of the cell cycle, maintaining genome stability.bioRxiv : the preprint server for biology · 2024Article
- Targeting DNA polymerase β elicits synthetic lethality with mismatch repair deficiency in acute lymphoblastic leukemia.Leukemia · 2023Article
- Ataxia Telangiectasia Mutated and MSH2 Control Blunt DNA End Joining in Ig Class Switch Recombination.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Loss of mismatch repair promotes a direct selective advantage in human stem cells.Stem cell reports · 2022Article
- Therapeutic Opportunities of Disrupting Genome Integrity in Adult Diffuse Glioma.Biomedicines · 2022Review
- Identification of LncRNA Prognostic Signature Associated With Genomic Instability in Pancreatic Adenocarcinoma.Frontiers in oncology · 2022Article
- Targeting mitochondrial DNA polymerase gamma for selective inhibition of MLH1 deficient colon cancer growth.PloS one · 2022Article
34 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Synthetic sickness/lethality (SSL) can be exploited to develop therapeutic strategies for cancer. Deficiencies in the tumor suppressor proteins MLH1 and MSH2 have been implicated in cancer. Here we demonstrate that deficiency in MSH2 is SSL with inhibition of the DNA polymerase POLB, whereas deficiency in MLH1 is SSL with DNA polymerase POLG inhibition. Both SSLs led to the accumulation of 8-oxoG oxidative DNA lesions. MSH2/POLB SSL caused nuclear 8-oxoG accumulation, whereas MLH1/POLG SSL led to a rise in mitochondrial 8-oxoG levels. Both SSLs were rescued by silencing the adenine glycosylase MUTYH, suggesting that lethality could be caused by the formation of lethal DNA breaks upon 8-oxoG accumulation. These data suggest targeted, mechanism-based therapeutic approaches.
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What OpenQuestion holds
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.