HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy

	HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy
	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
	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
内容类型	期刊论文
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.