ArticleThe Journal of clinical investigation2019
Ex vivo screen identifies CDK12 as a metastatic vulnerability in osteosarcoma.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 49 citations in OpenAlex.
- CDK12/CDK13 inhibition disrupts transcriptional elongation and replication fork progression in glioblastoma.EMBO molecular medicine · 2026Article
- CDK12 and CDK13 in oncology: from RNA regulation to therapeutic targeting.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- New insights into the dule roles CDK12 in human cancers: Mechanisms and interventions for cancer therapy.Journal of pharmaceutical analysis · 2025Review
- CDK12 inhibition enhances oxaliplatin efficacy in gastric cancer by suppressing the MAPK signaling pathway.Journal of gastrointestinal oncology · 2025Article
- Comprehensive multi-omics analysis of histone acetylation modulators identifies ASH1L as a novel aggressive marker for osteosarcoma.Discover oncology · 2025Article
- Development of CDK12 as a Cancer Therapeutic Target and Related Inhibitors.Current cancer drug targets · 2025Review
- CDK12 is a potential biomarker for diagnosis, prognosis and immunomodulation in pan-cancer.Scientific reports · 2024Article
- Osteosarcoma PDX-Derived Cell Line Models for Preclinical Drug Evaluation Demonstrate Metastasis Inhibition by Dinaciclib through a Genome-Targeted Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Temporal chromatin accessibility changes define transcriptional states essential for osteosarcoma metastasis.Nature communications · 2023Article
- Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities.Frontiers in oncology · 2023Review
- Precision oncology using ex vivo technology: a step towards individualised cancer care?Expert reviews in molecular medicine · 2022Review
- CDK12 orchestrates super-enhancer-associated CCDC137 transcription to direct hepatic metastasis in colorectal cancer.Clinical and translational medicine · 2022Article
- CYCLIN K down-regulation induces androgen receptor gene intronic polyadenylation, variant expression and PARP inhibitor vulnerability in castration-resistant prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
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- The establishment of CDK9/RNA PolII/H3K4me3/DNA methylation feedback promotes HOTAIR expression by RNA elongation enhancement in cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- StableFrontiers in oncology · 2022Article
- Discovery and resistance mechanism of a selective CDK12 degrader.Nature chemical biology · 2021Article
- Expression and prognostic value of transcription-associated cyclin-dependent kinases in human breast cancer.Aging · 2021Article
- Plasma Exosome-Derived Sentrin SUMO-Specific Protease 1: A Prognostic Biomarker in Patients With Osteosarcoma.Frontiers in oncology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Despite progress in intensification of therapy, outcomes for patients with metastatic osteosarcoma (OS) have not improved in thirty years. We developed a system that enabled preclinical screening of compounds against metastatic OS cells in the context of the native lung microenvironment. Using this strategy to screen a library of epigenetically targeted compounds, we identified inhibitors of CDK12 to be most effective, reducing OS cell outgrowth in the lung by more than 90% at submicromolar doses. We found that knockout of CDK12 in an in vivo model of lung metastasis significantly decreased the ability of OS to colonize the lung. CDK12 inhibition led to defects in transcription elongation in a gene length- and expression-dependent manner. These effects were accompanied by defects in RNA processing and altered the expression of genes involved in transcription regulation and the DNA damage response. We further identified OS models that differ in their sensitivity to CDK12 inhibition in the lung and provided evidence that upregulated MYC levels may mediate these differences. Our studies provided a framework for rapid preclinical testing of compounds with antimetastatic activity and highlighted CDK12 as a potential therapeutic target in OS.
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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.