Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy

被引：199

作者：

Li, Danan

Shimamura, Takeshi

Ji, Hongbin

Chen, Liang

Haringsma, Henry J.

McNamara, Kate

Liang, Mei-Chih

Perera, Samanthi A.

Zaghlul, Sara

Borgman, Christa L.

Kubo, Shigeto

Takahashi, Masaya

Sun, Yanping

Chirieac, Lucian R.

Padera, Robert F.

Lindeman, Neal I.

Janne, Pasi A.

Thomas, Roman K.

Meyerson, Matthew L.

Eck, Michael J.

Engelman, Jeffrey A.

Shapiro, Geoffrey I. ^{[1
]}

Wong, Kwok-Kin

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA

[3] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA

[4] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[7] Massachusetts Gen Hosp, Dept Med, Boston, MA 02129 USA

[8] Harvard Univ, Sch Med, Boston, MA 02129 USA

[9] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[10] Univ Cologne, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, Max Planck Soc, D-50931 Cologne, Germany

[11] Univ Cologne, Fac Med, D-50931 Cologne, Germany

[12] Univ Cologne, Ctr Integrated Oncol, D-50931 Cologne, Germany

[13] Broat Inst Harvard, Cambridge, MA 02141 USA

[14] MIT, Cambridge, MA 02141 USA

来源：

CANCER CELL | 2007年 / 12卷 / 01期

关键词：

D O I：

10.1016/j.ccr.2007.06.005

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The EGFR T790M mutation has been identified in tumors from lung cancer patients that eventually develop resistance to erlotinib. In this study, we generated a mouse model with doxycycline-inducible expression of a mutant EGFR containing both L858R, an erlotinib-sensitizing mutation, and the T790M resistance mutation (EGFR TL). Expression of EGFR TL led to development of peripheral adenocarcinomas with bronchioloalveolar features in alveoli as well as papillary adenocarcinomas in bronchioles. Treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI), HKI-272, shrunk only peripheral tumors but not bronchial tumors. However, the combination of HKI-272 and rapamycin resulted in significant regression of both types of lung tumors. This combination therapy may potentially benefit lung cancer patients with the EGFR T790M mutation.

引用

页码：81 / 93

页数：13

共 33 条

[1] Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR [J].