Format

Send to

Choose Destination
Clin Cancer Res. 2018 Apr 1;24(7):1734-1747. doi: 10.1158/1078-0432.CCR-17-2733. Epub 2018 Jan 12.

Personalized RNA Medicine for Pancreatic Cancer.

Author information

1
Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
2
Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts.
3
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology MIT, Cambridge, Massachusetts.
4
Marble Center for Cancer Nanomedicine, Massachusetts Institute of Technology, Cambridge, Massachusetts.
5
Beth Israel Deaconess Medical Center, Cancer Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts.
6
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
7
The division of Biomedical Informatics, The Department of Internal Medicine, College of Medicine, The University of Kentucky, Lexington, Kentucky.
8
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
9
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts.
10
Howard Hughes Medical Institute, Cambridge, Massachusetts.
11
Harvard Medical School Initiative for RNA Medicine, Department of Pathology, Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. fslack@bidmc.harvard.edu.

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. Clin Cancer Res; 24(7); 1734-47. ©2018 AACR.

PMID:
29330203
DOI:
10.1158/1078-0432.CCR-17-2733
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center