ArticleCell death & disease2020
Combined inhibition of JAK1/2 and DNMT1 by newly identified small-molecule compounds synergistically suppresses the survival and proliferation of cervical cancer cells.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 69 citations in OpenAlex.
- DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.International journal of molecular sciences · 2025Review
- Recent advances on gene-related DNA methylation in cancer diagnosis, prognosis, and treatment: a clinical perspective.Clinical epigenetics · 2025Review
- ATR regulates OCT4 phosphorylation and safeguards human naïve pluripotency.Scientific reports · 2025Article
- The power and the promise of epigenetic drugs in oncology.Frontiers in genetics · 2025Review
- Role of lncRNA TPRG1-AS1 in the development of cervical squamous cell carcinoma and its prognostic value.Discover oncology · 2024Article
- Targeting treatment resistance: unveiling the potential of RNA methylation regulators and TG-101,209 in pan-cancer neoadjuvant therapy.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Knockdown of RBM15 inhibits tumor progression and the JAK-STAT signaling pathway in cervical cancer.BMC cancer · 2023Article
- Acetylcholine promotes chronic stress-induced lung adenocarcinoma progression via α5-nAChR/FHIT pathway.Cellular and molecular life sciences : CMLS · 2023Article
- Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1.Chinese journal of integrative medicine · 2023Article
- Direct and indirect effects of IFN-α2b in malignancy treatment: not only an archer but also an arrow.Biomarker research · 2022Review
- Ruxolitinib attenuates secondary injury after traumatic spinal cord injury.Neural regeneration research · 2022Article
- An Epigenetic Role of Mitochondria in Cancer.Cells · 2022Review
- Regulated cell death (RCD) in cancer: key pathways and targeted therapies.Signal transduction and targeted therapy · 2022Review
- Review
- Expression and Clinical Significance of HER2 Gene and DNMT1 in Non-Small-Cell Lung Cancer.Disease markers · 2022Article
- Toll-like receptor 2 promotes breast cancer progression and resistance to chemotherapy.Oncoimmunology · 2022Article
- A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells.Frontiers in pharmacology · 2022Article
- Association Between SNPs in the One-Carbon Metabolism Pathway and the Risk of Female Breast Cancer in a Chinese Population.Pharmacogenomics and personalized medicine · 2022Article
- Epigenetics of Cutaneous Sarcoma.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite substantial advances in treating cervical cancer (CC) with surgery, radiation and chemotherapy, patients with advanced CC still have poor prognosis and significantly variable clinical outcomes due to tumor recurrence and metastasis. Therefore, to develop more efficacious and specific treatments for CC remains an unmet clinical need. In this study, by virtual screening the SPECS database, we identified multiple novel JAK inhibitor candidates and validated their antitumor drug efficacies that were particularly high against CC cell lines. AH057, the best JAK inhibitor identified, effectively blocked the JAK/STAT pathways by directly inhibiting JAK1/2 kinase activities, and led to compromised cell proliferation and invasion, increased apoptosis, arrested cell cycles, and impaired tumor progression in vitro and in vivo. Next, by screening the Selleck chemical library, we identified SGI-1027, a DNMT1 inhibitor, as the compound that displayed the highest synergy with AH057. By acting on a same set of downstream effector molecules that are dually controlled by JAK1/2 and DNMT1, the combination of AH057 with SGI-1027 potently and synergistically impaired CC cell propagation via dramatically increasing apoptotic cell death and cell-cycle arrest. These findings establish a preclinical proof of concept for combating CC by dual targeting of JAK1/2 and DNMT1, and provide support for launching a clinical trial to evaluate the efficacy and safety of this drug combination in patients with CC and other malignant tumors.
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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.