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

Ver/ Abrir
Fecha de publicación
2011Autor/a
Ni, Xiaohua
Zhang, Yonggang
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.
Metadatos
Mostrar el registro completo del ítemResumen
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.