ArticleExperimental & molecular medicine2022
DNA methylome and single-cell transcriptome analyses reveal CDA as a potential druggable target for ALK inhibitor-resistant lung cancer therapy.
Article in Experimental & molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 16 citations in OpenAlex.
- Single-Cell Transcriptomics of Pyrimidine Salvage in HBV-Related HCC Reveals Prognostic and Immune Infiltration Features.Biomolecules & therapeutics · 2026Article
- Deciphering the CAF‑LCN2 axis: Key to overcoming anti‑PD‑L1 immunotherapy resistance in lung cancer.International journal of molecular medicine · 2026Article
- scDrugMap: benchmarking large foundation models for drug response prediction.Nature communications · 2025Article
- Research trends in epigenetic studies on lung cancer: a bibliometric and visual analysis of the past decade.Journal of thoracic disease · 2025Article
- Empowering integrative and collaborative exploration of single-cell and spatial multimodal data with SGS genome browser.Cell genomics · 2025Article
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- DrugFormer: Graph-Enhanced Language Model to Predict Drug Sensitivity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Chemotherapy increases CDA expression and sensitizes malignant pleural mesothelioma cells to capecitabine treatment.Scientific reports · 2024Article
- Transcriptomic Approaches to Cardiomyocyte-Biomaterial Interactions: A Review.ACS biomaterials science & engineering · 2024Review
- Advances in single-cell omics and multiomics for high-resolution molecular profiling.Experimental & molecular medicine · 2024Review
- DRMref: comprehensive reference map of drug resistance mechanisms in human cancer.Nucleic acids research · 2024Article
- Integrative Analyses of Pyrimidine Salvage Pathway-Related Genes Revealing the Associations Between UPP1 and Tumor Microenvironment.Journal of inflammation research · 2024Article
- Advances in single-cell RNA sequencing and its applications in cancer research.Journal of hematology & oncology · 2023Review
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion-positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance, as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). Although drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the naïve cell population by scRNA-seq, and their abundance was increased in the acquired-resistance population. Knockdown of CDA had antiproliferative effects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2'-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC.
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