ArticleCell cycle (Georgetown, Tex.)2012
Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Clinical significance of DAPK promoter hypermethylation in lung cancer: a meta-analysis.Drug design, development and therapy · 2015Pooled it
- Review
- Targeting epigenetic regulators as a promising avenue to overcome cancer therapy resistance.Signal transduction and targeted therapy · 2025Review
- Recurrent and Metastatic Head and Neck Cancer: Mechanisms of Treatment Failure, Treatment Paradigms, and New Horizons.Cancers · 2025Review
- Review
- DNA Methylation as a Diagnostic, Prognostic, and Predictive Biomarker in Head and Neck Cancer.International journal of molecular sciences · 2023Review
- MonitoringFrontiers in oncology · 2023Review
- DNMT3A governs tyrosine kinase inhibitors responses through IAPs and in a cell senescence-dependent manner in non-small cell lung cancer.American journal of cancer research · 2023Article
- Review
- Predictive value of unmethylated RASSF1A on disease progression in non-small cell lung cancer patients receiving pemetrexed-based chemotherapy.Cancer biomarkers : section A of Disease markers · 2020Article
- Molecular Determinants of Cancer Therapy Resistance to HDAC Inhibitor-Induced Autophagy.Cancers · 2019Review
- Downregulation of DAPK1 promotes the stemness of cancer stem cells and EMT process by activating ZEB1 in colorectal cancer.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated Protein Kinase-Related Signals.International journal of molecular sciences · 2018Review
- Epigenomic profiling of non-small cell lung cancer xenografts uncover LRP12 DNA methylation as predictive biomarker for carboplatin resistance.Genome medicine · 2018Article
- Article
- Article
- Known and putative mechanisms of resistance to EGFR targeted therapies in NSCLC patients with EGFR mutations-a review.Translational lung cancer research · 2015Review
- Association between DNA methylation and multidrug resistance in human glioma SHG-44 cells.Molecular medicine reports · 2015Article
- Epigenetic changes associated with inflammation in breast cancer patients treated with chemotherapy.Brain, behavior, and immunity · 2014Article
- Phospho-ΔNp63α/microRNA network modulates epigenetic regulatory enzymes in squamous cell carcinomas.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Anti-EGFR therapy is among the most promising molecular targeted therapies against cancer developed in the past decade. However, drug resistance eventually arises in most, if not all, treated patients. Emerging evidence has linked epigenetic changes, such as DNA methylation at CpG islands, to the development of resistance to multiple anticancer drugs. In addition, genes that are differentially methylated have increasingly been appreciated as a source of clinically relevant biomarker candidates. To identify genes that are specifically methylated during the evolution of resistance to anti-EGFR therapeutic agents, we performed a methylation-specific array containing a panel of 56 genes that are commonly known to be regulated through promoter methylation in two parental non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC) cell lines and their resistant derivatives to either erlotinib or cetuximab. We found that death-associated protein kinase (DAPK) was hypermethylated in drug-resistant derivatives generated from both parental cell lines. Restoration of DAPK into the resistant NSCLC cells by stable transfection re-sensitized the cells to both erlotinib and cetuximab. Conversely, siRNA-mediated knockdown of DAPK induced resistance in the parental sensitive cells. These results demonstrate that DAPK plays important roles in both cetuximab and erlotinib resistance, and that gene silencing through promoter methylation is one of the key mechanisms of developed resistance to anti-EGFR therapeutic agents. In conclusion, DAPK could be a novel target to overcome resistance to anti-EGFR agents to improve the therapeutic benefit, and further evaluation of DAPK methylation as a potential biomarker of drug response is needed.
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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.