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Eliminación de residuos: una estrategia atractiva para el tratamiento del cáncer
Jemilat Salami1, Craig M Crews2,3,4
1Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Science (New York, N.Y.)
|March 18, 2017
Resumen
Este estudio introduce un nuevo enfoque de terapia contra el cáncer que utiliza la propia maquinaria de la célula para degradar las proteínas que causan cáncer, superando la resistencia a los medicamentos y apuntando a proteínas previamente no farmacológicas.
Área de la Ciencia:
- En el campo de la oncología
- Biología molecular
- La bioquímica
Sus antecedentes:
- Las terapias dirigidas al cáncer a menudo involucran pequeñas moléculas o anticuerpos que inhiben proteínas específicas que impulsan el crecimiento del tumor.
- Las células tumorales con frecuencia desarrollan resistencia a estas terapias, lo que limita la durabilidad del tratamiento.
- Muchas proteínas oncogénicas carecen de actividades enzimáticas o de receptores farmacológicos, lo que plantea un desafío para la terapia dirigida convencional.
Objetivo del estudio:
- Para presentar una estrategia alternativa de tratamiento dirigido.
- Aprovechar el sistema ubiquitina-proteasoma para la degradación selectiva de las proteínas que causan cáncer.
- Revisar los fármacos degradantes de proteínas existentes y los avances recientes en el diseño de nuevas moléculas pequeñas para la degradación de proteínas dirigidas.
Principales métodos:
- Revisión de los medicamentos contra el cáncer existentes que inducen la degradación de las proteínas.
- Discusión de los avances recientes en el diseño racional de moléculas pequeñas.
- Pruebas preclínicas de pequeñas moléculas para la degradación selectiva de proteínas objetivo.
Principales resultados:
- Identificación de medicamentos existentes que utilizan las vías de degradación de las proteínas.
- Avances en el diseño de pequeñas moléculas que inducen la degradación selectiva de las proteínas objetivo.
- Validación preclínica de nuevas estrategias dirigidas a la degradación de proteínas.
Conclusiones:
- La cooptación del sistema ubiquitina-proteasoma ofrece una alternativa prometedora a la terapia convencional dirigida al cáncer.
- Este enfoque puede superar la resistencia a los medicamentos y las proteínas objetivo previamente consideradas no farmacológicas.
- El diseño racional de moléculas pequeñas está avanzando en el campo de la degradación proteica dirigida para el tratamiento del cáncer.
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