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Un recurso interactivo para identificar las dependencias genéticas y de linaje del cáncer dirigidas por pequeñas
Amrita Basu1, Nicole E Bodycombe1, Jaime H Cheah1
1The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Cell
|September 3, 2013
Resumen
Los investigadores perfilaron 242 líneas de células cancerosas (CCL) para encontrar nuevos objetivos farmacológicos. Descubrieron un vínculo entre mutaciones genéticas específicas y sensibilidad a fármacos de moléculas pequeñas, ayudando a la terapia personalizada del cáncer.
Área de la Ciencia:
- La genómica es la genómica.
- Farmacología Farmacología.
- Biología del cáncer Biología del cáncer.
Sus antecedentes:
- Las terapias dirigidas muestran altas tasas de respuesta clínica en pacientes con cáncer con alteraciones genómicas específicas.
- Se está explorando el perfil de la línea celular del cáncer (CCL) para identificar nuevos biomarcadores para la sensibilidad a fármacos de pequeñas moléculas.
Objetivo del estudio:
- Para medir cuantitativamente la sensibilidad de 242 CCLs genómicamente caracterizadas a un conjunto de 354 pequeñas moléculas.
- Descubrir las dependencias de proteínas que se asocian con alteraciones genómicas específicas del cáncer y que pueden ser objeto de pequeñas moléculas.
- Crear un recurso para correlacionar las características genéticas con la sensibilidad a los fármacos y el control de los factores de confusión del perfil de la LCC.
Principales métodos:
- Medición de la sensibilidad cuantitativa de 242 líneas de células cancerosas (CCL) frente a 354 moléculas pequeñas.
- Caracterización genómica de las CCL probadas.
- Desarrollo del Portal de Respuesta a la Terapéutica del Cáncer (CTRP) para la correlación y el análisis de datos.
Principales resultados:
- Identificación de dependencias de proteínas vinculadas a alteraciones genómicas específicas del cáncer.
- Descubrimiento de asociaciones entre características genéticas y sensibilidad a pequeñas moléculas.
- Se encontró una dependencia candidata: las mutaciones activadoras en la β-catenina se correlacionan con la sensibilidad al navitoclax (un antagonista de la familia Bcl-2).
Conclusiones:
- El estudio proporciona un recurso valioso para identificar nuevas hipótesis terapéuticas.
- Los hallazgos aceleran el descubrimiento de fármacos adaptados a los pacientes con cáncer en función de su genotipo y linaje específicos.
- El Portal de Respuesta a la Terapéutica del Cáncer facilita la medicina personalizada al vincular los perfiles genéticos con las respuestas a los medicamentos.
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