ArticleJournal of experimental & clinical cancer research : CR2022
CDK7 inhibition augments response to multidrug chemotherapy in pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
16 citing papers in PubMed, 25 citations in OpenAlex.
- The Emerging Role of Transcription-Associated Cyclin-Dependent Kinases in Gastrointestinal Tumors.Cancers · 2026Review
- Identification of HSPE1 as a new actionable cancer vulnerability leads to an innovative and effective combination therapy for pancreatic ductal adenocarcinoma.Molecular cancer · 2026Article
- Targeting super-enhancer-driven SKIL transcription by CDK7 inhibitor THZ1 to suppress gastric cancer progression.Journal of translational medicine · 2026Article
- Novel niclosamide-derived Schiff bases as a dual-targeted anticancer agents.Scientific reports · 2026Article
- Article
- 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
- POC1A induces epithelial-mesenchymal transition to promote growth and metastasis through the STAT3 signaling pathway in triple-negative breast cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Current progress in targeting mitotic kinases in PDAC.RSC medicinal chemistry · 2025Review
- CRISPR/Cas technologies in pancreatic cancer research and therapeutics: recent advances and future outlook.Discover oncology · 2025Review
- Mechanistic Roles of Transcriptional Cyclin-Dependent Kinases in Oncogenesis: Implications for Cancer Therapy.Cancers · 2025Review
- High expression of SMPD4 promotes liver cancer and is associated with poor prognosis.BMC research notes · 2025Article
- Adenovirus vaccine targeting kinases induces potent antitumor immunity in solid tumors.Journal for immunotherapy of cancer · 2024Article
- Kinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues.Molecular oncology · 2024Article
- CDK7 in breast cancer: mechanisms of action and therapeutic potential.Cell communication and signaling : CCS · 2024Review
- Exploring Splicing Modulation as an Innovative Approach to Combat Pancreatic Cancer: SF3B1 Emerges as a Prognostic Indicator and Therapeutic Target.International journal of biological sciences · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a dismal prognosis. Although combined treatment with gemcitabine and albumin-bound paclitaxel has improved the prognosis of PDAC, both intrinsic and acquired chemoresistance remain as severe hurtles towards improved prognosis. Thus, new therapeutic targets and innovative strategies are urgently needed.
methodsIn this study, we used the KPC mouse model-derived PDAC cell line TB32047 to perform kinome-wide CRISPR-Cas9 loss-of-function screening. Next-generation sequencing and MAGeCK-VISPR analysis were performed to identify candidate genes. We then conducted cell viability, clonogenic, and apoptosis assays and evaluated the synergistic therapeutic effects of cyclin-dependent kinase 7 (CDK7) depletion or inhibition with gemcitabine (GEM) and paclitaxel (PTX) in a murine orthotopic pancreatic cancer model. For mechanistic studies, we performed genome enrichment analysis (GSEA) and Western blotting to identify and verify the pathways that render PDAC sensitive to GEM/PTX therapy.
resultsWe identified several cell cycle checkpoint kinases and DNA damage-related kinases as targets for overcoming chemoresistance. Among them, CDK7 ranked highly in both screenings. We demonstrated that both gene knockout and pharmacological inhibition of CDK7 by THZ1 result in cell cycle arrest, apoptosis induction, and DNA damage at least predominantly through the STAT3-MCL1-CHK1 axis. Furthermore, THZ1 synergized with GEM and PTX in vitro and in vivo, resulting in enhanced antitumor effects.
conclusionsOur findings support the application of CRISPR-Cas9 screening in identifying novel therapeutic targets and suggest new strategies for overcoming chemoresistance in pancreatic cancer.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.