HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy
文献类型：期刊论文
| 作者 | Perera, SA; Li, DA; Shimamura, T; Raso, MG; Ji, HB; Chen, LA; Borgman, CL; Zaghlul, S; Brandstetter, KA; Kubo, S |
| 刊名 | PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
 |
| 出版日期 | 2009 |
| 卷号 | 106期号:2页码:474-479 |
| 关键词 | lung cancer murine model |
| 通讯作者 | Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, 44 Binney St,D810, Boston, MA 02115 USA.,kwong1@partners.org |
| 英文摘要 | Mutations in the HER2 kinase domain have been identified in human clinical lung cancer specimens. Here we demonstrate that inducible expression of the most common HER2 mutant (HER2(YVMA)) in mouse lung epithelium causes invasive adenosquamous carcinomas restricted to proximal and distal bronchioles. Continuous expression of HER2YVMA is essential for tumor maintenance, suggesting a key role for HER2 in lung adenosquamous tumorigenesis. Preclinical studies assessing the in vivo effect of erlotinib, trastuzumab, BIBW2992, and/or rapamycin on HER2(YVMA) transgenic mice or H1781 xenografts with documented tumor burden revealed that the combination of BIBW2992 and rapamycin is the most effective treatment paradigm causing significant tumor shrinkage. Immunohistochemical analysis of lung tumors treated with BIBW2992 and rapamycin combination revealed decreased phosphorylation levels for proteins in both upstream and downstream arms of MAPK and Akt/mTOR signaling axes, indicating inhibition of these pathways. Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted. |
| 学科主题 | Science & Technology - Other Topics |
| 类目[WOS] | Multidisciplinary Sciences |
| 关键词[WOS] | HER2 KINASE DOMAIN ; ERBB RECEPTORS ; CANCER ; EGFR ; MUTATIONS ; TRASTUZUMAB ; ADENOCARCINOMAS ; ACTIVATION ; INHIBITORS ; CARCINOMA |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000262804000023 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1154]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Perera, SA,Li, DA,Shimamura, T,et al. HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2009,106(2):474-479. |
| APA | Perera, SA.,Li, DA.,Shimamura, T.,Raso, MG.,Ji, HB.,...&Wong, KK.(2009).HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,106(2),474-479. |
| MLA | Perera, SA,et al."HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106.2(2009):474-479. |
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