Epidermal growth factor receptor (EGFR) mutations in lung cancer: preclinical and clinical data
Braz. j. med. biol. res
;
47(11): 929-939, 11/2014. tab, graf
Artículo
en Inglés
| LILACS
| ID: lil-723897
ABSTRACT
Lung cancer leads cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC), the most prevalent subtype of this recalcitrant cancer, is usually diagnosed at advanced stages, and available systemic therapies are mostly palliative. The probing of the NSCLC kinome has identified numerous nonoverlapping driver genomic events, including epidermal growth factor receptor (EGFR) gene mutations. This review provides a synopsis of preclinical and clinical data on EGFR mutated NSCLC and EGFR tyrosine kinase inhibitors (TKIs). Classic somatic EGFR kinase domain mutations (such as L858R and exon 19 deletions) make tumors addicted to their signaling cascades and generate a therapeutic window for the use of ATP-mimetic EGFR TKIs. The latter inhibit these kinases and their downstream effectors, and induce apoptosis in preclinical models. The aforementioned EGFR mutations are stout predictors of response and augmentation of progression-free survival when gefitinib, erlotinib, and afatinib are used for patients with advanced NSCLC. The benefits associated with these EGFR TKIs are limited by the mechanisms of tumor resistance, such as the gatekeeper EGFR-T790M mutation, and bypass activation of signaling cascades. Ongoing preclinical efforts for treating resistance have started to translate into patient care (including clinical trials of the covalent EGFR-T790M TKIs AZD9291 and CO-1686) and hold promise to further boost the median survival of patients with EGFR mutated NSCLC.
Texto completo:
Disponible
Índice:
LILACS (Américas)
Asunto principal:
Proteínas Tirosina Quinasas
/
Carcinoma de Pulmón de Células no Pequeñas
/
Receptores ErbB
/
Neoplasias Pulmonares
/
Mutación
Tipo de estudio:
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Braz. j. med. biol. res
Asunto de la revista:
Biologia
/
Medicina
Año:
2014
Tipo del documento:
Artículo
/
Documento de proyecto
País de afiliación:
Estados Unidos
Institución/País de afiliación:
Harvard Medical School/US
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