ArticleJCI insight2022
VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 57 citations in OpenAlex.
- SERPINI1 functions as a tumor suppressor in glioma.Scientific reports · 2026Article
- Structure-based discovery of selective vaccinia-related kinase 1 inhibitors and fluorogenic active-site probes.The Journal of biological chemistry · 2026Article
- VRK1 Is a Novel Therapeutic Target for Small Cell Neuroendocrine Carcinoma of the Cervix.Cancer science · 2026Article
- Barrier-to-Autointegration Factor 1: a key regulator of nuclear envelope integrity, genome stability, and disease progression.Frontiers in immunology · 2026Review
- Cancer-Type-Specific DNA Methylation Is a Source of Vulnerability in Liver Cancer Cells.Cancer science · 2025Article
- VRK1 promotes epithelial-mesenchymal transition in hepatocellular carcinoma mediated by SNAI1 via phosphorylating CHD1L.Cell death & disease · 2025Article
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Targeting the Sodium-Potassium Pump as a Therapeutic Strategy in Acute Myeloid Leukemia.Cancer research · 2024Article
- Developmental origins shape the paediatric cancer genome.Nature reviews. Cancer · 2024Review
- Advances in synthetic lethality modalities for glioblastoma multiforme.Open medicine (Warsaw, Poland) · 2024Review
- Genome-Wide CRISPR Screens Identify Multiple Synthetic Lethal Targets That Enhance KRASG12C Inhibitor Efficacy.Cancer research · 2023Article
- 2D and 3D multiplexed subcellular profiling of nuclear instability in human cancer.bioRxiv : the preprint server for biology · 2023Article
- The pattern of histone H3 epigenetic posttranslational modifications is regulated by the VRK1 chromatin kinase.Epigenetics & chromatin · 2023Article
- Paralog-based synthetic lethality: rationales and applications.Frontiers in oncology · 2023Review
- VRK3 depletion induces cell cycle arrest and metabolic reprogramming of pontine diffuse midline glioma - H3K27 altered cells.Frontiers in oncology · 2023Article
- Synthetic lethal interactions of DEAD/H-box helicases as targets for cancer therapy.Frontiers in oncology · 2022Review
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 4 institutions in 2 countries.
Funding
Abstract
Collateral lethality occurs when loss of a gene/protein renders cancer cells dependent on its remaining paralog. Combining genome-scale CRISPR/Cas9 loss-of-function screens with RNA sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase vaccinia-related kinase 1 (VRK1) for their survival in vivo. VRK1 dependency was inversely correlated with expression of its paralog VRK2. VRK2 knockout sensitized cells to VRK1 loss, and conversely, VRK2 overexpression increased cell fitness in the setting of VRK1 loss. DNA methylation of the VRK2 promoter was associated with low VRK2 expression in human neuroblastomas and adult and pediatric gliomas. Mechanistically, depletion of VRK1 reduced barrier-to-autointegration factor phosphorylation during mitosis, resulting in DNA damage and apoptosis. Together, these studies identify VRK1 as a synthetic lethal target in VRK2 promoter-methylated adult and pediatric gliomas and neuroblastomas.
Indexed as
Identifiers
What Socratic 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 Socratic graph.