Los inhibidores de la tirosina quinasa afectan el sabor dulce y desregulan la selección del destino de subtipos específicos de células gustativas a través de la inhibición de KIT
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Ver abstracta en PubMed
Resumen
Este resumen es generado por máquina.Los efectos secundarios de los medicamentos contra el cáncer, como la pérdida del gusto, pueden derivarse del bloqueo de la señalización de KIT. Esto bloquea las receptoras tirosinokinasas (RTK), alterando el desarrollo y la función de las células gustativas, lo que lleva a una percepción reducida del sabor dulce.
Área De La Ciencia
- Neurociencia del gusto
- Biología molecular
- Farmacología del cáncer
Sus Antecedentes
- La disfunción del gusto (disgeusia) es un efecto secundario frecuente de los inhibidores antiangiogénicos de la tirosina quinasa (ITC) utilizados en el tratamiento del cáncer.
- Los mecanismos precisos que vinculan las TKI con la disgeusia siguen sin estar claros, en parte debido a la comprensión limitada de las receptoras tirosinokinasas (RTK) en la homeostasis del gusto en adultos.
Objetivo Del Estudio
- Investigar el papel de las RTK en la homeostasis del gusto en adultos.
- Aclarar los mecanismos por los que las TKI inducen la disfunción del gusto.
Principales Métodos
- Administración del TKI cabozantinib en ratones adultos.
- Ensayos conductuales para evaluar las respuestas al gusto.
- Nocaut inducible del RTK KIT en ratones.
Principales Resultados
- El tratamiento con cabozantinib alteró las vías de diferenciación de los subtipos funcionales de células gustativas en ratones.
- Los ratones tratados con TKI mostraron una respuesta disminuida a los sabores dulces.
- La alteración genética de la señalización de KIT imitaba en gran medida los efectos del tratamiento con cabozantinib.
Conclusiones
- El RTK KIT se identifica como un regulador clave de la homeostasis de las células gustativas en ratones adultos.
- El bloqueo de la señalización de KIT por TKI se propone como un mecanismo potencial subyacente a la disgeusia inducida por TKI en pacientes con cáncer.
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