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Proyecto DRIVE: Un compendio de las dependencias del cáncer y las relaciones letales sintéticas descubiertas por la
E Robert McDonald1, Antoine de Weck1, Michael R Schlabach1
1Novartis Institutes for Biomedical Research, Oncology Disease Area, Basel 4002, Switzerland; Cambridge, MA 02139, USA; and Emeryville, CA 94608, USA.
Cell
|July 29, 2017
Resumen
Este estudio traza las dependencias del cáncer mediante el cribado de 7.837 genes en 398 líneas celulares de cáncer. Los hallazgos identifican nuevos objetivos terapéuticos para el tratamiento del cáncer, especialmente para la pérdida de genes supresores de tumores.
Área de la Ciencia:
- Biología del cáncer
- La genómica
- Descubrimiento de drogas
Sus antecedentes:
- Los avances en la comprensión de las mutaciones del cáncer han llevado a terapias específicas.
- Sin embargo, la identificación de vulnerabilidades relacionadas con la pérdida de genes supresores de tumores sigue siendo un desafío.
Objetivo del estudio:
- Realizar una prueba de interferencia de ARN (RNAi) a gran escala para identificar las dependencias del cáncer.
- Descubrir nuevos objetivos terapéuticos para varios subtipos de cáncer, particularmente aquellos que involucran la pérdida de genes supresores de tumores.
Principales métodos:
- Se realizó una prueba de detección de ARNi a gran escala en 398 líneas de células cancerosas.
- Se evaluaron los efectos de viabilidad de derribar 7.837 genes utilizando un promedio de 20 ARN de horquilla corta (shRNA) por gen.
Principales resultados:
- Clases identificadas de genes de dependencia del cáncer y sus correlaciones con características genéticas, de expresión y de linaje.
- Redes de interacción de genes caracterizadas, incluidos los complejos de proteínas y la cooperación de vías.
- Se creó un conjunto de datos completo y un portal web para uso de la comunidad.
Conclusiones:
- El estudio proporciona un recurso valioso para descubrir y traducir nuevas terapias contra el cáncer.
- Las dependencias identificadas ofrecen objetivos potenciales para contrarrestar la pérdida de genes supresores de tumores y mejorar las estrategias de tratamiento del cáncer.
Palabras clave:
El CCLE¿Qué es eso?Interferencia del ARNDependencia del cáncergenómica funcionalletalidad sintéticaMás Videos Relacionados
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