Personalized RNA Medicine for Pancreatic Cancer
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; Slack, Frank J.; ... Show more Show less
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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.
Date issued
2018-01Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science; Koch Institute for Integrative Cancer Research at MITJournal
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
ISSN
1078-0432
1557-3265