ArticleMolecular cancer2021
Targeting CDK7 suppresses super enhancer-linked inflammatory genes and alleviates CAR T cell-induced cytokine release syndrome.
Article in Molecular cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 27 citations in OpenAlex.
- Super-enhancer-driven SGK1 activates polyamine metabolism to promote autoimmune uveitis.Science advances · 2026Article
- Carbon ion irradiation at a clinically used dose rewires super-enhancers to drive necroptosis and systemic immunity.Science advances · 2026Article
- Pharmacological inhibition of CDK7 and CDK9 suppresses gastrointestinal (colon) cancer progression through modulation of stemness, epithelial-mesenchymal transition, and chemoresistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Disrupting MED8-dependent epigenetic reprogramming augments avapritinib sensitivity in PDGFRA-driven glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Discovery of a selective CDK7 PROTAC against acute leukemia with low platelet toxicity.Leukemia · 2026Article
- A robust and scalable immunoadsorbent platform based on the high-affinity M03-IgG antibody for targeted IL-6 Removal in cytokine storm.Frontiers in immunology · 2026Article
- Transcriptome Analysis, Machine Learning, and Experimental Identification of CDK7 Affecting the Progression of Pregnancy-induced Hypertension by Influencing Macrophage Polarization.Current molecular medicine · 2026Article
- Latest updates on pathogenesis mechanisms and management strategies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis related to CAR-T cell therapies.Annals of hematology · 2025Review
- Advances and challenges in CAR-T cell therapy for head and neck squamous cell carcinoma.Biomarker research · 2025Review
- Article
- Super-enhancers in immune system regulation: mechanisms, pathological reprogramming, and therapeutic opportunities.Frontiers in immunology · 2025Review
- Herpes simplex virus 1 inhibits phosphorylation of RNA polymerase II CTD serine-7.Journal of virology · 2024Article
- Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors.Journal for immunotherapy of cancer · 2024Article
- Effects of super-enhancers in cancer metastasis: mechanisms and therapeutic targets.Molecular cancer · 2024Review
- Inflammatory microenvironment regulation and osteogenesis promotion by bone-targeting calcium and magnesium repletion nanoplatform for osteoporosis therapy.Journal of nanobiotechnology · 2024Article
- Genetic Susceptibility in Endothelial Injury Syndromes after Hematopoietic Cell Transplantation and Other Cellular Therapies: Climbing a Steep Hill.Current issues in molecular biology · 2024Review
- Advancing CAR T cell therapy through the use of multidimensional omics data.Nature reviews. Clinical oncology · 2023Review
- Advances in CAR-T Cell Therapy in Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2023Review
- Review
- Transcription associated cyclin-dependent kinases as therapeutic targets for prostate cancer.Oncogene · 2022Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCytokine release syndrome (CRS) is a systemic inflammatory response characterized by the overexpression of inflammatory genes. Controlling CRS is essential for improving the therapeutic effects of chimeric antigen receptor (CAR) engineered T cells. However, current treatment options are limited given the complexity of cytokine interactions so it is important to seek a mild strategy with broad-spectrum inhibition to overcome this challenge.
methodsUsing THZ1, a covalent inhibitor of cyclin-dependent kinase 7 (CDK7), we demonstrated the transcriptional suppression of inflammatory genes in activated macrophages. RNA sequencing and ChIP sequencing were conducted to identify the key target genes of the inflammatory response. Pathogen- and CAR T cell-induced CRS models were also established to assess the efficacy and safety of targeting CDK7.
resultsCDK7 blockade attenuated cytokine release, mitigated hyperinflammatory states and rescued mice from lethal CRS. Targeting CDK7 preferentially suppressed a set of inflammatory genes, of which STAT1 and IL1 were the key targets associated with super enhancers. Furthermore, we confirmed the potent efficacy of THZ1 in alleviating the CRS induced by CAR T cell infusion without causing tissue injury or impairing antitumor effects.
conclusionsOur work indicates the CDK7-dependent transcription addiction of inflammatory genes. Targeting CDK7 is a promising strategy for treating CRS by inhibiting multiple cytokines.
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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.