Detalle Publicación

ARTÍCULO
YES1 Drives Lung Cancer Growth and Progression and Predicts Sensitivity to Dasatinib
Autores: Garmendia, Irati; Pajares Villandiego, María José; Hermida-Prado, F.; Ajona Martínez-Polo, Daniel; Bértolo Martín de Rosales, Cristina María; Sainz, Cristina; Lavín Remón, Amaya; Remírez, Ana; Valencia Leoz, Karmele; Moreno, Haritz; Ferrer, I.; Bherens, C.; Cuadrado, M.; Paz-Ares, L.; Soxe, Bustelo; Gil Bazo, Ignacio; Alameda Serrano, Daniel; Lecanda Cordero, Fernando; Calvo González, Alfonso; Felip, E.; Montse, Sánchez-Cèspedes; Wistuba, I.; R. Grada-Díaz; J.P. Rodrigo; J. M. García-Pedrero; Pio Osés, Rubén; Montuenga Badía, Luis (Autor de correspondencia); Agorreta Arrazubi, Jackeline
Título de la revista: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
ISSN: 1073-449X
Volumen: 200
Número: 7
Páginas: 888 - 899
Fecha de publicación: 2019
Resumen:
Rationale: The characterization of new genetic alterations is essential to assign effective personalized therapies in non-small cell lung cancer (NSCLC). Furthermore, finding stratification biomarkers is essential for successful personalized therapies. Molecular alterations of YES1, a member of the SRC (proto-oncogene tyrosine-protein kinase Src) family kinases (SFKs), can be found in a significant subset of patients with lung cancer.Objectives: To evaluate YES1 (v-YES-1 Yamaguchi sarcoma viral oncogene homolog 1) genetic alteration as a therapeutic target and predictive biomarker of response to dasatinib in NSCLC.Methods: Functional significance was evaluated by in vivo models of NSCLC and metastasis and patient-derived xenografts. The efficacy of pharmacological and genetic (CRISPR [clustered regularly interspaced short palindromic repeats]/Cas9 [CRISPR-associated protein 9]) YES1 abrogation was also evaluated. In vitro functional assays for signaling, survival, and invasion were also performed. The association between YES1 alterations and prognosis was evaluated in clinical samples.