Mecanismos de resistencia al trastuzumab

Ernesto Korbenfeld

doi:10.56969/oc.v17i1.130

Autores/as

Ernesto Korbenfeld Servicio de Oncología Clínica, Hospital Británico de Buenos Aires https://orcid.org/0000-0001-6343-9991

DOI:

https://doi.org/10.56969/oc.v17i1.130

Palabras clave:

trastuzumab, cáncer de mama, Her2, mecanismo de acción, resistencia, revisión, breast cancer, mechanism of action, resistance, review

Resumen

El trastuzumab es un anticuerpo monoclonal dirigido contra el receptor del factor de crecimiento epidérmico humano (Her2), el cual se encuentra sobreexpresado en aproximadamente el 20% del cáncer de mama invasivo. El trastuzumab es un claro ejemplo de exitoso desarrollo de terapia “blanco específica” en oncología y actualmente se encuentra aprobado para su uso terapéutico en cáncer de mama Her2+ tanto en enfermedad avanzada como con criterio adyuvante. Sin embargo, alrededor del 50% de las pacientes con cáncer de mama Her2+ no se benefician de las terapias basadas en trastuzumab. El entendimiento de los mecanismos de acción y de resistencia al trastuzumab es crucial para el desarrollo de nuevas estrategias de tratamiento. Los mecanismos de resistencia al trastuzumab se pueden agrupar en 4 categorías principales: A. Obstáculos para la unión del trastuzumab al dominio extracelular del Her2. B. Activación de las vías de traducción de señales río abajo del Her2. C. Activación de vías alternativas del Her2. D. Fallas del sistema inmunitario para destruir las células tumorales. Esta revisión resume las evidencias preclínicas y clínicas acerca de los mecanismos de acción y resistencia al trastuzumab y también discute el desarrollo de nuevas drogas antiHer2 y sus posibles implicancias clínicas.

Citas

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