Amplification of EGFR Wild-Type Alleles in Non-Small Cell Lung Cancer Cells Confers Acquired Resistance to Mutation-Selective EGFR Tyrosine Kinase Inhibitors.
Cancer Res
; 77(8): 2078-2089, 2017 04 15.
Article
en En
| MEDLINE
| ID: mdl-28202511
ABSTRACT
EGFR-mutated lung cancers account for a significant subgroup of non-small cell lung cancers overall. Third-generation EGFR tyrosine kinase inhibitors (TKI) are mutation-selective inhibitors with minimal effects on wild-type EGFR. Acquired resistance develops to these agents, however, the mechanisms are as yet uncharacterized. In this study, we report that the Src-AKT pathway contributes to acquired resistance to these TKI. In addition, amplification of EGFR wild-type alleles but not mutant alleles was sufficient to confer acquired resistance. These findings underscore the importance of signals from wild-type EGFR alleles in acquiring resistance to mutant-selective EGFR-TKI. Our data provide evidence of wild-type allele-mediated resistance, a novel concept of acquired resistance in response to mutation-selective inhibitor therapy in cancer treatment. Cancer Res; 77(8); 2078-89. ©2017 AACR.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
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Inhibidores de Proteínas Quinasas
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Receptores ErbB
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Neoplasias Pulmonares
Tipo de estudio:
Clinical_trials
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Prognostic_studies
Límite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cancer Res
Año:
2017
Tipo del documento:
Article
País de afiliación:
Japón