ArticleOncogene2019
Thymine DNA glycosylase as a novel target for melanoma.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 42 citations in OpenAlex.
- Positive TAZ-TDG feedback loop drives proneural-to-mesenchymal transition to promote glioblastoma progression.Journal of translational medicine · 2026Article
- Targeting transcriptional plasticity in cancer.Nature chemical biology · 2026Article
- Targeting thymine DNA glycosylase induces synthetic lethality in p53-deficient cancers.Nature chemical biology · 2026Article
- The dark side of the light (UVA): melanoma microenvironment and cell survival strategies.Cell death discovery · 2025Article
- The TET-TDG axis in T cells and biological processes.International immunology · 2025Review
- Multi-regional genomic and transcriptomic characterization of a melanoma-associated oral cavity cancer provide evidence for CASP8 alteration-mediated field cancerization.Human genomics · 2024Article
- Genetic effects on the skin methylome in healthy older twins.American journal of human genetics · 2024Article
- Detection of Uracil-Excising DNA Glycosylases in Cancer Cell Samples Using a Three-Dimensional DNAzyme Walker.ACS measurement science au · 2024Article
- Epigenetic modulators provide a path to understanding disease and therapeutic opportunity.Genes & development · 2024Review
- Base Excision Repair: Mechanisms and Impact in Biology, Disease, and Medicine.International journal of molecular sciences · 2023Review
- Chimeric d/l-DNA Probes of Base Excision Repair Enable Real-Time Monitoring of Thymine DNA Glycosylase Activity in Live Cells.Journal of the American Chemical Society · 2023Article
- Thymine DNA glycosylase mediates chromatin phase separation in a DNA methylation-dependent manner.The Journal of biological chemistry · 2023Article
- TET1 and TDG Suppress Inflammatory Response in Intestinal Tumorigenesis: Implications for Colorectal Tumors With the CpG Island Methylator Phenotype.Gastroenterology · 2023Article
- DNA methylation regulator-based signature for predicting clear cell renal cell carcinoma prognosis.American journal of translational research · 2023Article
- Computational investigations on target-site searching and recognition mechanisms by thymine DNA glycosylase during DNA repair process.Acta biochimica et biophysica Sinica · 2022Review
- Energy Landscapes for Base-Flipping in a Model DNA Duplex.The journal of physical chemistry. B · 2022Article
- Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime.Scientific reports · 2022Article
- The Role of Thymine DNA Glycosylase in Transcription, Active DNA Demethylation, and Cancer.Cancers · 2022Review
- Roles of TET and TDG in DNA demethylation in proliferating and non-proliferating immune cells.Genome biology · 2021Article
- Review
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 6 institutions in 3 countries.
Funding
Abstract
Melanoma is an aggressive neoplasm with increasing incidence that is classified by the NCI as a recalcitrant cancer, i.e., a cancer with poor prognosis, lacking progress in diagnosis and treatment. In addition to conventional therapy, melanoma treatment is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints. As drug resistance remains a major obstacle to treatment success, advanced therapeutic approaches based on novel targets are still urgently needed. We reasoned that the base excision repair enzyme thymine DNA glycosylase (TDG) could be such a target for its dual role in safeguarding the genome and the epigenome, by performing the last of the multiple steps in DNA demethylation. Here we show that TDG knockdown in melanoma cell lines causes cell cycle arrest, senescence, and death by mitotic alterations; alters the transcriptome and methylome; and impairs xenograft tumor formation. Importantly, untransformed melanocytes are minimally affected by TDG knockdown, and adult mice with conditional knockout of Tdg are viable. Candidate TDG inhibitors, identified through a high-throughput fluorescence-based screen, reduced viability and clonogenic capacity of melanoma cell lines and increased cellular levels of 5-carboxylcytosine, the last intermediate in DNA demethylation, indicating successful on-target activity. These findings suggest that TDG may provide critical functions specific to cancer cells that make it a highly suitable anti-melanoma drug target. By potentially disrupting both DNA repair and the epigenetic state, targeting TDG may represent a completely new approach to melanoma therapy.
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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.