ArticleOncogene2019
THZ1 reveals CDK7-dependent transcriptional addictions in pancreatic cancer.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The trial behind it
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Who cites it
42 citing papers in PubMed, 85 citations in OpenAlex.
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Genome-Wide CRISPR/Cas9 Screening Identifies Modulators of THZ1 Response in Acute Myeloid Leukemia.Biomedicines · 2026Article
- The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors.Cancers · 2026Review
- CDK7-targeted therapy effectively disrupts cell cycle progression and oncogenic signaling in head and neck cancer.Signal transduction and targeted therapy · 2025Article
- Novel Pyrazolo [1,5-a]-1,3,5-Triazine Derivatives as CDK7 Inhibitors: Synthesis and Biological Insights in Pancreatic Ductal Adenocarcinoma Models.ChemMedChem · 2025Article
- Recent advances in development of CDK7 inhibitors and their clinical trials: a narrative review.Translational cancer research · 2025Review
- Current progress in targeting mitotic kinases in PDAC.RSC medicinal chemistry · 2025Review
- Enhancer regulation in cancer: from epigenetics to mArchives of pharmacal research · 2025Review
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- Super-Enhancer Reprograming Driven by SOX9 and TCF7L2 Represents Transcription-Targeted Therapeutic Vulnerability for Treating Gallbladder Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.Neuro-oncology · 2024Article
- Inhibition of cyclin-dependent kinase 7 mitigates doxorubicin cardiotoxicity and enhances anticancer efficacy.Cardiovascular research · 2024Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Co-overexpression of BRD4 and CDK7 promotes cell proliferation and predicts poor prognosis in HCC.Heliyon · 2024Article
- CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties.Signal transduction and targeted therapy · 2023Article
- Super-enhancer-driven lncRNA LIMD1-AS1 activated by CDK7 promotes glioma progression.Cell death & disease · 2023Article
- CDK12/13 promote splicing of proximal introns by enhancing the interaction between RNA polymerase II and the splicing factor SF3B1.Nucleic acids research · 2023Article
- Article
- Superenhancers as master gene regulators and novel therapeutic targets in brain tumors.Experimental & molecular medicine · 2023Review
- Widespread hypertranscription in aggressive human cancers.Science advances · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy with high mortality. Lack of effective treatment makes novel therapeutic discovery an urgent demand in PDAC research. By screening an epigenetic-related compound library, we identified THZ1, a covalent inhibitor of CDK7, as a promising candidate. Multiple long-established and patient-derived PDAC cell lines (PDC) were used to validate the efficacy of THZ1 in vitro. In addition, patient-derived xenograft (PDX) models and animal models of PDAC were utilized for examining THZ1 efficacy in vivo. Furthermore, RNA-Seq analyse was performed to reveal the molecular mechanism of THZ1 treatment. Finally, PDAC cell lines with primary or acquired resistance to THZ1 were investigated to explore the potential mechanism of THZ1 susceptibility. CDK7 inhibition was identified as a selective and potent therapeutic strategy for PDAC progression in multiple preclinical models. Mechanistic analyses revealed that CDK7 inhibition led to a pronounced downregulation of gene transcription, with a preferential repression of mitotic cell cycle and NF-κB signaling-related transcripts. MYC transcriptional was found to be involved in susceptibility of PDAC cells to CDK7 inhibition. In conclusion, Identification of CDK7-dependent transcriptional addiction in PDACs provides a potent therapeutic strategy that targets highly aggressive pancreatic cancer.
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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.