Rapamycin prevents the development and progression of mutant epidermal growth factor receptor lung tumors with the acquired resistance mutation T790M Journal Article
| Authors: | Kawabata, S.; Mercado-Matos, J.; Hollander, M.; Donahue, D.; Wilson, W.; Regales, L.; Butaney, M.; Pao, W.; Wong, K. K.; Jänne, P.; Dennis, P. A. |
| Article Title: | Rapamycin prevents the development and progression of mutant epidermal growth factor receptor lung tumors with the acquired resistance mutation T790M |
| Abstract: | Lung cancer in never-smokers is an important disease often characterized by mutations in epidermal growth factor receptor (EGFR), yet risk reduction measures and effective chemopreventive strategies have not been established. We identify mammalian target of rapamycin (mTOR) as potentially valuable target for EGFR mutant lung cancer. mTOR is activated in human lung cancers with EGFR mutations, and this increases with acquisition of T790M mutation. In a mouse model of EGFR mutant lung cancer, mTOR activation is an early event. As a single agent, the mTOR inhibitor rapamycin prevents tumor development, prolongs overall survival, and improves outcomes after treatment with an irreversible EGFR tyrosine kinase inhibitor (TKI). These studies support clinical testing of mTOR inhibitors in order to prevent the development and progression of EGFR mutant lung cancers. © 2014 The Authors. |
| Keywords: | cancer survival; controlled study; human cell; overall survival; drug efficacy; protein function; biological marker; mammalia; lung non small cell cancer; epidermal growth factor receptor; carcinogenesis; loading drug dose; lung tumor; cancer inhibition; survival time; drug mechanism; mammalian target of rapamycin; tumor growth; doxycycline; rapamycin; epidermal growth factor receptor kinase inhibitor; human; priority journal; article |
| Journal Title: | Cell Reports |
| Volume: | 7 |
| Issue: | 6 |
| ISSN: | 2211-1247 |
| Publisher: | Cell Press |
| Date Published: | 2014-06-26 |
| Start Page: | 1824 |
| End Page: | 1832 |
| Language: | English |
| DOI: | 10.1016/j.celrep.2014.05.039 |
| PROVIDER: | scopus |
| PMCID: | PMC4110638 |
| PUBMED: | 24931608 |
| DOI/URL: | |
| Notes: | Export Date: 1 August 2014 -- Source: Scopus |
