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Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts

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Fecha de publicación
2011
Autor/a
Ni, Xiaohua
Zhang, Yonggang
Ribas i Fortuny, Judit
Chowdhury, Wasim H.
Castanares, Mark
Zhang, Zhewei
Laiho, Marikki
DeWeese, Theodore L.
Lupold, Shawn E.
Cita recomendada
Ni, Xiaohua; Zhang, Yonggang; Ribas i Fortuny, Judit; Chowdhury, Wasim H.; Castanares, Mark; Zhang, Zhewei; ... Lupold, Shawn E.. (2011) . Prostate-targeted radiosensitization via aptamer-shRNA chimeras in human tumor xenografts. Journal of Clinical Investigation, 2011, vol. 121, núm. 6, p. 2383-2390. https://doi.org/10.1172/JCI45109.
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Resumen
Dose-escalated radiation therapy for localized prostate cancer (PCa) has a clear therapeutic benefit; however, escalated doses may also increase injury to noncancerous tissues. Radiosensitizing agents can improve ionizing radiation (IR) potency, but without targeted delivery, these agents will also sensitize surrounding normal tissues. Here we describe the development of prostate-targeted RNAi agents that selectively sensitized prostate-specific membrane antigen–positive (PSMA-positive) cells to IR. siRNA library screens identified DNA-activated protein kinase, catalytic polypeptide (DNAPK) as an ideal radiosensitization target. DNAPK shRNAs, delivered by PSMA-targeting RNA aptamers, selectively reduced DNAPK in PCa cells, xenografts, and human prostate tissues. Aptamer-targeted DNAPK shRNAs, combined with IR, dramatically and specifically enhanced PSMA-positive tumor response to IR. These findings support aptamer-shRNA chimeras as selective sensitizing agents for the improved treatment of high-risk localized PCa.
URI
http://hdl.handle.net/10459.1/47333
DOI
https://doi.org/10.1172/JCI45109
Es parte de
Journal of Clinical Investigation, 2011, vol. 121, núm. 6, p. 2383-2390
Proyectos de investigación europeos
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  • Articles publicats (Medicina Experimental) [330]
  • Articles publicats (Grup de Recerca en Neurobiologia Cel·lular) [19]
  • Articles publicats (IRBLleida) [1083]

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