Vinculan nueva terapia para el cáncer con problemas cardiovasculares severos
MADRID. Un nuevo estudio en ratones constata que el uso prolongado de los inhibidores de Plk1, una terapia innovadora contra el cáncer de leucemia aún en fase de ensayo clínico, puede producir no solo problemas de hipertensión arterial sino también rotura de vasos sanguíneos y problemas cardiovasculares severos.
El trabajo liderado por españoles señala que los inhibidores Plk1 pueden provocar también aneurismas y roturas aórticas.
Estas son las principales conclusiones de un estudio publicado en la revista Nature Medicine, cuyos autores apuntan que los resultados pueden tener “importantes implicaciones” en el desarrollo de estos nuevos tratamientos, por eso sugieren una revisión de los protocolos de uso.
Plk1 fue inicialmente caracterizada como una proteína que controla cómo las células se multiplican, por lo que se vio en ella una nueva diana terapéutica para frenar el crecimiento tumoral, señala el Centro Nacional de Investigaciones Oncológicas (CNIO).
Varios inhibidores de esta proteína se encuentran en ensayos clínicos para diversos tipos de tumores, como “volasertib”, que recibió recientemente el reconocimiento de “Terapia innovadora en leucemias” por la Agencia Reguladora del Medicamento de EEUU (FDA), por su eficacia contra la leucemia mieloide aguda.
Este medicamento está dentro de lo que se conoce como medicina personalizada, basada en conocer la función de cada uno los genes y proteínas y seleccionar los fármacos adecuados contra estas según las alteraciones de cada paciente.
Sin embargo, tal y como afirma Marcos Malumbres, coordinador del estudio y jefe del Grupo de División Celular y Cáncer del CNIO, uno de los problemas con los que se encuentran al ensayar con nuevos fármacos en pacientes es que todavía se conoce muy poco de la función real de las proteínas a las que van dirigidos.
En mamíferos
Por eso, su equipo quiso estudiar la función real de Plk1 en mamíferos usando como modelo ratones, afirma el CNIO en su nota.
Para estudiar la función de Plk1, los científicos generaron una variante de ratón con niveles disminuidos de esa proteína.
“Fue sorprendente, la mitad de los ratones fallecían de hemorragias torácicas debidas a la rotura de las arterias”, explica Guillermo de Cárcer, también del CNIO.
Uno de los resultados más llamativos, según Cárcer, es que los machos morían la primera noche que pasaban con hembras en la misma caja -una de las situaciones que provoca la mayor subida de tensión arterial-.
“Nuestros datos no van en contra del uso de estos inhibidores en la clínica”, asegura Malumbres, quien añade: “desgraciadamente, todos los fármacos tienen efectos secundarios, el problema es no conocerlos”.
Malumbres indicó que en el estudio probaron el efecto con tres fármacos y todos ellos dieron los mismos resultados en células en cultivo y han testado dos en ratones también con el mismo resultado.
Existen, al menos, ocho inhibidores de Plk1 desarrollados por distintas compañías en ensayos clínicos en leucemias y diversos tipos de tumores sólidos, pero volasertib es el más avanzado de ellos en su desarrollo clínico, agregó.
Sin embargo, “no podemos descartar -dijo- que los problemas cardiovasculares sean diferentes con unos u otros inhibidores”.
Además del CNIO, participaron el Centro Nacional de Investigaciones Cardiovasculares, el Centro de Investigación del Cáncer en Salamanca y el London Research Institute.
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