Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M

Shigeru Kawabata, José R. Mercado-Matos, M. Christine Hollander, Danielle Donahue, Willie Wilson, Lucia Regales, Mohit Butaney, William Pao, Kwok Kin Wong, Pasi A. Jänne, Phillip A. Dennis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1824-1832
Number of pages9
JournalCell Reports
Volume7
Issue number6
DOIs
StatePublished - Jun 26 2014

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Sirolimus
Epidermal Growth Factor Receptor
Tumors
Lung Neoplasms
Lung
Mutation
Neoplasms
Risk Reduction Behavior
Protein-Tyrosine Kinases
Chemical activation
Survival
Testing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kawabata, S., Mercado-Matos, J. R., Hollander, M. C., Donahue, D., Wilson, W., Regales, L., ... Dennis, P. A. (2014). Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M. Cell Reports, 7(6), 1824-1832. https://doi.org/10.1016/j.celrep.2014.05.039

Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M. / Kawabata, Shigeru; Mercado-Matos, José R.; Hollander, M. Christine; Donahue, Danielle; Wilson, Willie; Regales, Lucia; Butaney, Mohit; Pao, William; Wong, Kwok Kin; Jänne, Pasi A.; Dennis, Phillip A.

In: Cell Reports, Vol. 7, No. 6, 26.06.2014, p. 1824-1832.

Research output: Contribution to journalArticle

Kawabata, S, Mercado-Matos, JR, Hollander, MC, Donahue, D, Wilson, W, Regales, L, Butaney, M, Pao, W, Wong, KK, Jänne, PA & Dennis, PA 2014, 'Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M', Cell Reports, vol. 7, no. 6, pp. 1824-1832. https://doi.org/10.1016/j.celrep.2014.05.039
Kawabata, Shigeru ; Mercado-Matos, José R. ; Hollander, M. Christine ; Donahue, Danielle ; Wilson, Willie ; Regales, Lucia ; Butaney, Mohit ; Pao, William ; Wong, Kwok Kin ; Jänne, Pasi A. ; Dennis, Phillip A. / Rapamycin Prevents the Development and Progression of Mutant Epidermal Growth Factor Receptor Lung Tumors with the Acquired Resistance Mutation T790M. In: Cell Reports. 2014 ; Vol. 7, No. 6. pp. 1824-1832.
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