ArticleCancer gene therapy2009
MLH1 deficiency enhances tumor cell sensitivity to ganciclovir.
Article in Cancer gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.bioRxiv : the preprint server for biology · 2026Article
- RAD18- and BRCA1-dependent pathways promote cellular tolerance to the nucleoside analog ganciclovir.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Article
- Inhibition of homologous recombination with vorinostat synergistically enhances ganciclovir cytotoxicity.DNA repair · 2013Article
- Depletion of deoxyribonucleotide pools is an endogenous source of DNA damage in cells undergoing oncogene-induced senescence.The American journal of pathology · 2013Article
- Unrepairable DNA double-strand breaks initiate cytotoxicity with HSV-TK/ganciclovir.Cancer gene therapy · 2011Article
- Alteration of the carbohydrate for deoxyguanosine analogs markedly changes DNA replication fidelity, cell cycle progression and cytotoxicity.Mutation research · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Suicide gene therapy with herpes simplex virus thymidine kinase (HSV-TK) and ganciclovir (GCV) is notable for producing multi-log cytotoxicity in a unique pattern of delayed cytotoxicity in S-phase. As hydroxyurea, a ribonucleotide reductase inhibitor that activates mismatch repair, can increase sensitivity to GCV, we evaluated the role of MLH1, an essential mismatch repair protein, in GCV cytotoxicity. Using HCT116TK (HSV-TK-expressing) colon carcinoma cells that express or lack MLH1, cell-survival studies demonstrated greater GCV sensitivity in the MLH1-deficient cells, primarily at high concentrations. This could not be explained by differences in GCV metabolism, as the less sensitive MLH1-expresssing cells accumulated more GCV triphosphate and incorporated more of the analog into DNA. SiRNA suppression of MLH1 in U251 glioblastoma or SW480 colon carcinoma cells also enhanced sensitivity to high concentrations of GCV. Studies in a pa nel of yeast deletion mutants confirmed the results with MLH1, and further suggested a role for homologous recombination repair and several cell-cycle checkpoint proteins in GCV cytotoxicity. These data suggest that MLH1 can prevent cytotoxicity with GCV. Targeting mismatch repair-deficient tumors may increase efficacy of this suicide gene therapy approach to cancer treatment.
Indexed as
Identifiers
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.