دورية أكاديمية
Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors
| العنوان: | Intact regulation of G1/S transition renders esophageal squamous cell carcinoma sensitive to PI3Kα inhibitors |
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| المؤلفون: | Xu Zhang, Yuxiang Wang, Xi Zhang, Yanyan Shen, Kang Yang, Qingyang Ma, Yuemei Qiao, Jiajie Shi, Yi Wang, Lan Xu, Biyu Yang, Gaoxiang Ge, Landian Hu, Xiangyin Kong, Chunhao Yang, Yi Chen, Jian Ding, Linghua Meng |
| المصدر: | Signal Transduction and Targeted Therapy, Vol 8, Iss 1, Pp 1-14 (2023) |
| بيانات النشر: | Nature Publishing Group, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Biology (General) |
| مصطلحات موضوعية: | Medicine, Biology (General), QH301-705.5 |
| الوصف: | Abstract Phosphatidylinositol 3-kinase alpha (PI3Kα) inhibitors are currently evaluated for the therapy of esophageal squamous cell carcinoma (ESCC). It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3Kα inhibitors in an aim to improve the clinical responsive rate in ESCC. Here, ESCC PDXs with CCND1 amplification were found to be more sensitive to CYH33, a novel PI3Kα-selective inhibitor currently in clinical trials for the treatment of advanced solid tumors including ESCC. Elevated level of cyclin D1, p21 and Rb was found in CYH33-sensitive ESCC cells compared to those in resistant cells. CYH33 significantly arrested sensitive cells but not resistant cells at G1 phase, which was associated with accumulation of p21 and suppression of Rb phosphorylation by CDK4/6 and CDK2. Hypo-phosphorylation of Rb attenuated the transcriptional activation of SKP2 by E2F1, which in turn hindered SKP2-mediated degradation of p21 and reinforced accumulation of p21. Moreover, CDK4/6 inhibitors sensitized resistant ESCC cells and PDXs to CYH33. These findings provided mechanistic rationale to evaluate PI3Kα inhibitors in ESCC patients harboring amplified CCND1 and the combined regimen with CDK4/6 inhibitors in ESCC with proficient Rb. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2059-3635 |
| Relation: | https://doaj.org/toc/2059-3635 |
| DOI: | 10.1038/s41392-023-01359-x |
| URL الوصول: | https://doaj.org/article/334f2a57e34f491b8c4c6cdba5a34ed0 |
| رقم الأكسشن: | edsdoj.334f2a57e34f491b8c4c6cdba5a34ed0 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20593635 |
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| DOI: | 10.1038/s41392-023-01359-x |