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

Overview

abstract

  • 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.

publication date

  • July 1, 2007

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Bronchial Neoplasms
  • ErbB Receptors
  • Lung Neoplasms
  • Mutation

Identity

Scopus Document Identifier

  • 34347208648

Digital Object Identifier (DOI)

  • 10.1016/j.ccr.2007.06.005

PubMed ID

  • 17613438

Additional Document Info

volume

  • 12

issue

  • 1