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Investigadores españoles crean estrategia para identificar dianas terapéuticas en cáncer de mama triple negativo El cáncer de mama triple negativo es el más agresivo y afecta a entre el 15 y el 20% de todas las mujeres afectadas.
El cáncer de mama es el que más sufren las mujeres en el mundo más sufren las mujeres en el mundo . Una investigación liderada por el doctor Atanasio Pandiella y financiada por CRIS contra el cáncer ha diseñado una estrategia para identificar dianas terapéuticas en cáncer de mama triple negativo , el más agresivo y que representa entre el 15 y el 20% de todos los casos de cáncer de mama .
La estrategia para identificar dianas terapéuticas en el cáncer de mama más agresivo , se basa analizar el surfaceoma , que son proteínas de la superficie celular. Debido a su ubicación en la superficie de la célula , son accesibles, y la expresión de alguna de ellas está alterada en diversos tipos de cáncer.
De hecho, algunas de esas proteínas están 'sobreexpresadas', o sea, su cantidad es mucho mayor en la célula tumoral que en una célula normal. Esto permite actuar preferentemente sobre la célula tumoral utilizando, por ejemplo, anticuerpos específicos contra esa proteína.
En la actualidad, existen diferentes estrategias terapéuticas que utilizan como diana las proteínas de la superficie celular. Entre estas se encuentran los anticuerpos conjugados a fármacos (ADCs). Los ADCs son anticuerpos a los cuales se les ha pegado un agente tóxico para la célula . Por tanto, estos fármacos suman el efecto antitumoral del anticuerpo y el efecto antitumoral del fármaco que llevan pegado.
En concreto, el grupo al que pertenece Pandiella, del Centro de Investigación del Cáncer y del Servicio de Anatomía Patológica del Hospital Universitario de Salamanca, y al que CRIS contra el cáncer financia, se propuso identificar nuevas dianas para ADCs que podrían usarse para este subtipo de cáncer de mama.
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Una veintena de proteínas podrían ser dianas terapéuticas de los anticuerpos conjugados Este estudio llevó a la identificación de un grupo de unas 20 proteínas que podían ser dianas de ADCs. Estudios posteriores focalizaron el interés en una de ellas, denominada CD98hc. Frente a esta proteína, se preparó en el laboratorio un anticuerpo conjugado a fármaco (ADC).
En la siguiente fase, se realizaron experimentos 'in vitro', es decir, se han empleado líneas celulares de cáncer de mama triple negativo. "En estos estudios, se observó que este ADC poseía una potente y específica actividad antitumoral frente a células de cáncer de mama triple negativo", explica el investigador Juan Carlos Montero, del Centro de Investigación del Cáncer-IBSAL-Hospital Clínico Universitario de Salamanca, que también ha dirigido la investigación.
El ADC contra la proteína CD98hc no solo bloqueó la progresión del ciclo celular (impidió que las células tumorales se expandiesen ), sino que acabó provocando también muerte de las células tumorales.
Para profundizar en el efecto antitumoral observado del ADC contra CD98hc, se llevaron a cabo nuevos experimentos. En esta ocasión, se trabajó con modelos experimentales 'in vivo', es decir, se comprobó este efecto antitumoral del ADC de CD98hc en ratonas con tumores creados en ellas tras inyectarles células humanas de cáncer de mama triple negativo. De esta manera, se comprobó que el ADC contra la proteína CD98hc reducía el volumen tumoral en el animal.
En definitiva, resalta Pandiella, "estos resultados preclínicos abren la puerta a la posibilidad de explorar la eficacia de ADCs dirigidos frente a CD98hc en la clínica". Por otro lado, cabe la posibilidad de que la proteína CD98hc se sobreexprese también en otros tipos de tumores.
Si este fuera el caso, extendería aún más el valor de este trabajo, ya que abriría la posibilidad de usar la proteína CD98hc como una nueva diana terapéutica de ADC para la terapia de otros tipos de cáncer. Por último, el uso de esta estrategia para identificar proteínas de la superficie celular diferencialmente expresadas en los tumores permite establecer las bases para definir nuevas dianas potenciales de ADCs en otros tumores sólidos o hematológicos.
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