ArticleCancer research and treatment2020
Inhibition of ATR Increases the Sensitivity to WEE1 Inhibitor in Biliary Tract Cancer.
Article in Cancer research and treatment, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 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
19 citing papers in PubMed, 21 citations in OpenAlex.
- Prognostic, Predictive, and Clinical Relevance of DNA Damage Repair Alterations in Biliary Tract Cancers.Cancers · 2026Review
- Senescence-associated secretory phenotype in lung cancer: remodeling the tumor microenvironment for metastasis and immune suppression.Frontiers in oncology · 2025Review
- Combination of S-1 and the oral ATR inhibitor ceralasertib is effective against pancreatic cancer cells.Cancer chemotherapy and pharmacology · 2024Article
- Immunomodulatory effects of trastuzumab deruxtecan through the cGAS-STING pathway in gastric cancer cells.Cell communication and signaling : CCS · 2024Article
- Current and Future Therapeutic Targets for Directed Molecular Therapies in Cholangiocarcinoma.Cancers · 2024Review
- Article
- Combined Inhibition of Smoothened and the DNA Damage Checkpoint WEE1 Exerts Antitumor Activity in Cholangiocarcinoma.Molecular cancer therapeutics · 2023Article
- Targeting replication stress in cancer therapy.Nature reviews. Drug discovery · 2023Review
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Multiple-low-dose therapy: effective killing of high-grade serous ovarian cancer cells with ATR and CHK1 inhibitors.NAR cancer · 2022Article
- DNA Damage Response Inhibitors in Cholangiocarcinoma: Current Progress and Perspectives.Cells · 2022Review
- ATR inhibitor AZD6738 increases the sensitivity of colorectal cancer cells to 5‑fluorouracil by inhibiting repair of DNA damage.Oncology reports · 2022Article
- Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer.Cancer research and treatment · 2022Article
- HJURP Promotes Malignant Progression and Mediates Sensitivity to Cisplatin and WEE1-inhibitor in Serous Ovarian Cancer.International journal of biological sciences · 2022Article
- Enrichment of Wee1/CDC2 and NF-κB Signaling Pathway Constituents Mutually Contributes to CDDP Resistance in Human Osteosarcoma.Cancer research and treatment · 2022Article
- Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation.Cancers · 2021Review
- The Role of the Hedgehog Pathway in Cholangiocarcinoma.Cancers · 2021Review
- Article
- Targeting P53 as a Future Strategy to Overcome Gemcitabine Resistance in Biliary Tract Cancers.Biomolecules · 2020Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeCurrently, the DNA damage response (DDR) pathway represents a key target for new cancer drug development. Advanced biliary tract cancer (BTC) has a poor prognosis because of the lack of efficacious treatment options. Although DNA repair pathway alterations have been reported in many patients with BTC, little is known regarding the effects of DDR-targeted agents against BTC. MATERIALS AND
methodsIn this study, nine BTC cell lines were exposed to the WEE1 inhibitor (AZD1775). In vitro, MTT assay, colony-forming assay, cell cycle analysis, phospho-histone H3 staining assay, Transwell migration assay, and western blot were performed. Then, to enhance the antitumor effect of AZD1775, the combination treatment of WEE1 inhibitor and ataxia telangiectasia mutated and Rad3 related (ATR) inhibitor (AZD6738) was conducted using MTT assay and comet assay. Finally, HuCCT-1 and SNU2670 xenograft models were established to confirm the anti-tumor effect of AZD1775 alone. Furthermore, the combination treatment was also evaluated in SNU2670 xenograft models.
resultsAZD1775 blocked the phosphorylation of CDC2 and CDC25C in all cell lines, but significantly increased apoptosis and S phase arrest in sensitive cells. However, increased p-ATR and phosphorylated ataxia telangiectasia mutated levels were observed in less sensitive cells. In addition, in vitro and in vivo data illustrated that AZD1775 combined with AZD6738 exerted more potent anti-tumor effects than either drug alone. Although WEE1 inhibition has promising anti-tumor effects in some BTC cells, the addition of ATR inhibitors could enhance its efficacy.
conclusionTaken together, this study supports further clinical development of DDR-targeted strategies as monotherapy or combination regimens for BTC.
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