AI Article Synopsis
- The study focuses on developing personalized medicine strategies using RNA-based therapeutics by leveraging patient-derived organoid (PDO) and patient-derived xenograft (PDX) models to predict responses in pancreatic cancer.
- Researchers performed microRNA profiling to identify disruptions in individual patient profiles, which informed the creation of targeted treatments.
- The use of tumor-penetrating nanocomplexes for delivering therapies showed promise in reducing tumor growth in both PDO and PDX models, setting the stage for potential clinical applications tailored to specific patient characteristics.
Article Abstract
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. 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. 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. 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. .
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| http://dx.doi.org/10.1158/1078-0432.CCR-17-2733 | DOI Listing |
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