Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3K alpha-selective inhibitor CYH33 in breast cancer
文献类型：期刊论文
| 作者 | Liu, Xue-ling2,3; Xu, Yi-chao2; Wang, Yu-xiang2,3; Chen, Yi2 ; Wang, Bo-bo2; Wang, Yi2; Chen, Yan-hong3; Tan, Cun3; Hu, Lan-ding1; Ma, Qing-yang1
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| 刊名 | CANCER LETTERS
 |
| 出版日期 | 2018 |
| 卷号 | 433页码:273-282 |
| 关键词 | PIK3CA HER2 Akt Patient-derived xenograft (PDX) |
| ISSN号 | 0304-3835 |
| DOI | 10.1016/j.canlet.2018.07.011 |
| 文献子类 | Article |
| 英文摘要 | PI3Ks are frequently hyper-activated in breast cancer and targeting PI3K alpha has exhibited promising but variable response in preclinical and clinical settings. CYH33 is a novel PI3K alpha-selective inhibitor in phase I clinical trial. We investigated the efficacy of CYH33 against breast cancer and explored potential predictive biomarkers. CYH33 potently restrained tumor growth in mice bearing human breast cancer cell xenografts and in R26-Pik3ca (H1047R);MMTV-Cre transgenic mice. CYH33 significantly inhibited proliferation of a panel of human breast cancer cells, while diversity in sensitivity has been observed. Cells harboring activating PIK3CA mutation, amplified HER2 were more responsive to CYH33 than their counterparts. Besides, cells in HER2-enriched or luminal subtype were more sensitive to CYH33 than basal-like breast cancer. Sensitivity to CYH33 has been further revealed to be associated with induction of G1 phase arrest and simultaneous inhibition of Akt and ERK. Sensitivity of patient-derived xenograft to CYH33 was also positively correlated with decrease in phosphorylated ERK. Taken together, CYH33 is a promising PI3K alpha inhibitor for breast cancer treatment and decrease in ERK phosphorylation may indicate its efficacy, which provides useful clues for rational design of the ongoing clinical trials. |
| WOS关键词 | PI3K/AKT/MTOR PATHWAY INHIBITORS ; PI3K ; TRIALS ; SENSITIVITY ; BIOMARKERS ; RESISTANCE ; LESSONS |
| 资助项目 | "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020218] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2018ZX09711002-011] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000441489500027 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272302]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Ding, Jian; Meng, Ling-hua |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Stem Cell Biol, Shanghai, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Dept Med Chem, Shanghai, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Xue-ling,Xu, Yi-chao,Wang, Yu-xiang,et al. Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3K alpha-selective inhibitor CYH33 in breast cancer[J]. CANCER LETTERS,2018,433:273-282. |
| APA | Liu, Xue-ling.,Xu, Yi-chao.,Wang, Yu-xiang.,Chen, Yi.,Wang, Bo-bo.,...&Meng, Ling-hua.(2018).Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3K alpha-selective inhibitor CYH33 in breast cancer.CANCER LETTERS,433,273-282. |
| MLA | Liu, Xue-ling,et al."Decrease in phosphorylated ERK indicates the therapeutic efficacy of a clinical PI3K alpha-selective inhibitor CYH33 in breast cancer".CANCER LETTERS 433(2018):273-282. |
入库方式： OAI收割
来源：上海药物研究所
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