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LAS CÉLULAS TUMORALES CAMBIAN PARA DISEMINARSE
Los patrones epigenéticos de las células metastásicas son distintos a los de las células tumorales primarias, según los resultados de los últimos trabajos de investigación del grupo que dirige Manel Esteller en el Programa de Epigenética y Biología del Cáncer del Instituto de Investigación Biomédica de Bellvitge (Idibell), que se presentan estos días en la Conferencia sobre Metástasis y Angiogénesis que organiza dicho centro en Barcelona.
Las variaciones en el epigenoma de las células tumorales son parte de la estrategia que siguen primero para escaparse del tumor primario, luego para diseminarse y finalmente para anidar en el nuevo tejido, ha explicado Esteller a Diario Médico.
“No se trata de un cambio radical en el epigenoma; son variaciones sutiles, pero podemos comprobar que las células se han modulado para adaptarse al nuevo ambiente y crecer”.
Profundizar en el estudio de estos pequeños cambios será de gran utilidad para descubrir las estrategias moleculares que siguen estas células en el proceso de metástasis y así buscar nuevas vías para intentar evitar o detener el proceso.Según los estudios del grupo que encabeza Esteller en el Idibell, el tumor primario es capaz de desactivar unos genes que le adhieren a las células vecinas.
“Entonces las células dejan de estar ancladas y se escapan, pero cuando llegan al ganglio ahí necesitan desengancharse otra vez para crecer, por lo que vuelven a desmetilarse esos genes y cuando el tumor ya ha crecido suficiente vuelve a cambiar para producir la siguiente metástasis distal”, ha detallado.
Fármacos específicos
Los hallazgos sobre las variaciones epigenéticas entre las células tumorales durante las diferentes etapas del proceso de metástasis serán de utilidad en la búsqueda de nuevos fármacos específicos orientados a evitar la diseminación tumoral. Este mismo grupo de investigación ya había demostrado en estudios previos que algunos medicamentos genéticos, como los agentes desmetilantes del ADN o los inhibidores de las histonas desacetilasas, son capaces de inhibir la metástasis en modelos celulares y murinos.
“Son fármacos que actualmente están aprobados para tratar neoplasias hematológicas y hemos visto que in vitro son capaces de inhibir la angiogénesis y la diseminación de los tumores”.
El mecanismo de acción de estos fármacos se centra en evitar que se produzcan los factores angiogénicos, lo que impide que el tumor sea irrigado y alimentado correctamente, por lo que detiene su crecimiento y si no sigue produciendo neovasos al final sufre necrosis y puede morir.
Estas moléculas se dirigen contra los receptores de los factores de crecimiento de los vasos, pero ahora se podrían buscar nuevos medicamentos epigenéticos dirigidos contra los mecanismos que regulan tales factores de crecimiento.Una de las hipótesis que surgen de estos hallazgos es que los fármacos epigenéticos pudieran potenciar a los actuales antiangiogénicos.
CONTROL DEL MICROAMBIENTE
Raghu Kalluri, de la Harvard Medical School (Estados Unidos), ha presentado los resultados de sus últimos trabajos que apuntan a la importancia del estroma en la actividad tumoral. Estos datos ponen de relieve que las nuevas terapias deben tener en cuenta a este microambiente para tratar de impedir que el entorno sea propicio para el crecimiento tumoral.
Por su parte, Kari Alitalo, de la Universidad de Helsinki (Finlandia), estudia la linfangiogénesis y ha explicado que, si se consigue evitar el crecimiento de los conductos linfáticos, el tumor tiende a intoxicarse y a morir. En opinión de Esteller, se trata de una vía de estudio interesante, ya que la metástasis suele afectar primero a los ganglios linfáticos que rodean al tumor.
Fuente: www.diariomedico.com
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