Personalized RNA Medicine for Pancreatic Cancer
Name
c79ff439f793519e5fe077bcf055d17b5f5f.pdf
Description
Accepted version
Size
9.7 MB
Format
Adobe PDF
Checksum (MD5)
c9d17cbaa1b1983505ae7be0306939c2
Author(s)
Gilles, Maud-Emmanuelle
Hao, Liangliang
Huang, Ling
Rupaimoole, Rajesha
Lopez-Casas, Pedro P.
Pulver, Emilia M
Jeong, Jong Cheol
Muthuswamy, Senthil K.
Hidalgo, Manuel
Bhatia, Sangeeta N
Date Issued
January 2018
Journal
Clincical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Citation
Gilles, Maud-Emmanuelle et al. "Personalized RNA Medicine for Pancreatic Cancer." Clincical Cancer Research 24, 7 (January 2018): 1734-1747 © 2018 American Association for Cancer Research
Version
Author's final manuscript
Abstract
Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21, was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-Noncommercial-Share Alike
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1158/1078-0432.ccr-17-2733
