27 noviembre 2013
Joan Massagué dirigirá el mejor centro mundial contra el cáncer . El catalán acaba de ser elegido director científico del Sloan-Kettering de Nueva York .
Los referentes de la oncología mundial hablan español. Si hace ya tiempo que los investigadores españoles en cáncer están reconocidos entre los mejores del mundo, este crédito se ve ahora avalado por su nombramiento como responsables de los mejores centros de investigación internacionales. La última designación le ha llegado al biólogo barcelonés Joan Massagué, que acaba de ser elegido director científico del Sloan-Kettering de Nueva York, el programa sobre el estudio del cáncer más importante de Estados Unidos y uno de los más prestigiosos del mundo.La institución es el brazo científico del Memorial Sloan-Kettering Center de Nueva York, considerado como el mejor hospital oncológico del mundo, junto al M.D. Anderson de Texas, y que tiene como director médico desde el pasado 1 de enero a otro español, Joan Baselga.
Massagué, considerado como el auténtico referente mundial en metástasis, trabajaba desde 1989 en la institución de Nueva York como jefe de los programas de Biología Molecular y de Biología Genética. «Massagué es un científico ejemplar y un líder internacional en el estudio de la metástasis del cáncer y los factores de crecimiento que regulan el comportamiento celular», subrayó Craig B. Thompson, consejero delegado del centro. El investigador catalán dirigirá un equipo de más de 900 investigadores y gestionará un presupuesto de 250 millones de euros anuales. Además de sus funciones directivas seguirá dedicado a la investigación. «Aquí sería inadmisible que el director no fuera también un investigador», según explicó en declaraciones a La Vanguardia. «Estar implicado en la investigación activa -añadió- es la única manera de mantenerse al día de los rápidos avances que se producen hoy en día en biomedicina».
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Yondelis Combinado con SN38 son Sinérgicos y Activos para el Tratamiento del Sarcoma de EWING . Dual targeting of EWS-FLI1 activity and the associated DNA damage response with Trabectedin and SN38 synergistically inhibits Ewing sarcoma cell growth .
SN-38 is the active metabolite of irinotecan (an analog of camptothecin - a topoisomerase I inhibitor); it is 1000 times more active than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold.
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Published OnlineFirst November 25, 2013 .
Conclusions:
These results provide the basis and rationale for translating this drug combination to the clinic. In addition, the study highlights an approach that utilizes a targeted agent to interfere with an oncogenic transcription factor and then exploits the resulting changes in gene expression to develop a molecularly targeted combination therapy.
Abstract :
Purpose: The goal of this study is to optimize the activity of trabectedin for Ewing sarcoma by developing a molecularly targeted combination therapy. Experimental Design: We have recently shown that trabectedin interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. In this report, we build on this work to develop a trabectedin based combination therapy with improved EWS-FLI1 suppression that also targets the drug associated DNA damage to ES cells.
Results: We demonstrate by siRNA experiments that EWS-FLI1 drives the expression of the Werner Syndrome protein (WRN) in ES cells. Since WRN deficient cells are known to be hypersensitive to camptothecins, we utilize trabectedin to block EWS-FLI1 activity, suppress WRN expression and selectively sensitize ES cells to the DNA damaging effects of SN38. We show that trabectedin and SN38 are synergistic, demonstrate an increase in DNA double strand breaks, an accumulation of cells in S-phase and a low picomolar IC50. In addition, SN38 cooperates with trabectedin to augment the suppression of EWS-FLI1 downstream targets, leading to an improved therapeutic index in vivo.
These effects translate into the marked regression of two Ewing sarcoma xenografts at a fraction of the dose of camptothecin used in other xenograft studies.
Copyright © 2013, American Association for Cancer Research.
*******************************************
Published OnlineFirst November 25, 2013 .Conclusions:
These results provide the basis and rationale for translating this drug combination to the clinic. In addition, the study highlights an approach that utilizes a targeted agent to interfere with an oncogenic transcription factor and then exploits the resulting changes in gene expression to develop a molecularly targeted combination therapy.
Abstract :
Purpose: The goal of this study is to optimize the activity of trabectedin for Ewing sarcoma by developing a molecularly targeted combination therapy. Experimental Design: We have recently shown that trabectedin interferes with the activity of EWS-FLI1 in Ewing sarcoma cells. In this report, we build on this work to develop a trabectedin based combination therapy with improved EWS-FLI1 suppression that also targets the drug associated DNA damage to ES cells.
Results: We demonstrate by siRNA experiments that EWS-FLI1 drives the expression of the Werner Syndrome protein (WRN) in ES cells. Since WRN deficient cells are known to be hypersensitive to camptothecins, we utilize trabectedin to block EWS-FLI1 activity, suppress WRN expression and selectively sensitize ES cells to the DNA damaging effects of SN38. We show that trabectedin and SN38 are synergistic, demonstrate an increase in DNA double strand breaks, an accumulation of cells in S-phase and a low picomolar IC50. In addition, SN38 cooperates with trabectedin to augment the suppression of EWS-FLI1 downstream targets, leading to an improved therapeutic index in vivo.
These effects translate into the marked regression of two Ewing sarcoma xenografts at a fraction of the dose of camptothecin used in other xenograft studies.
Copyright © 2013, American Association for Cancer Research.