@article{9f7c8b0317704ef3b71aea9e81b8c1f4,
title = "Nanoparticle-Based Follistatin Messenger RNA Therapy for Reprogramming Metastatic Ovarian Cancer and Ameliorating Cancer-Associated Cachexia",
abstract = "This study presents the first messenger RNA (mRNA) therapy for metastatic ovarian cancer and cachexia-induced muscle wasting based on lipid nanoparticles that deliver follistatin (FST) mRNA predominantly to cancer clusters following intraperitoneal administration. The secreted FST protein, endogenously synthesized from delivered mRNA, efficiently reduces elevated activin A levels associated with aggressive ovarian cancer and associated cachexia. By altering the cancer cell phenotype, mRNA treatment prevents malignant ascites, delays cancer progression, induces the formation of solid tumors, and preserves muscle mass in cancer-bearing mice by inhibiting negative regulators of muscle mass. Finally, mRNA therapy provides synergistic effects in combination with cisplatin, increasing the survival of mice and counteracting muscle atrophy induced by chemotherapy and cancer-associated cachexia. The treated mice develop few nonadherent tumors that are easily resected from the peritoneum. Clinically, this nanomedicine-based mRNA therapy can facilitate complete cytoreduction, target resistance, improve resilience during aggressive chemotherapy, and improve survival in advanced ovarian cancer.",
keywords = "cachexia, lipid nanoparticles, mRNA therapy, muscle atrophy, ovarian cancer",
author = "Tetiana Korzun and Moses, {Abraham S.} and Jeonghwan Kim and Siddharth Patel and Canan Schumann and Levasseur, {Peter R.} and Parham Diba and Brennan Olson and Rebola, {Katia Graziella De Oliveira} and Mason Norgard and Youngrong Park and Demessie, {Ananiya A.} and Yulia Eygeris and Vladislav Grigoriev and Subisha Sundaram and Tanja Pejovic and Brody, {Jonathan R.} and Taratula, {Olena R.} and Xinxia Zhu and Gaurav Sahay and Marks, {Daniel L.} and Oleh Taratula",
note = "Funding Information: This work was supported by the National Cancer Institute of the National Institutes of Health under Award Nos. R37CA234006 and R01CA237569, OHSU Knight Cancer Institute, and Friends of Doernbecher. Support was also received from the College of Pharmacy at Oregon State University, Pap{\'e} Family Pediatric Research Institute at Oregon Health & Science University, and ARCS Scholarship (The Karen Irons Medicis Memorial Scholar Award, Diane and Dick Alexander). The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. The electron microscopy was performed using the Multiscale Microscopy Core (MMC) at Oregon Health & Science University with technical support from the (OHSU)‐FEI Living Lab and the Center for Spatial Systems Biomedicine (OCSSB). Funding Information: This work was supported by the National Cancer Institute of the National Institutes of Health under Award Nos. R37CA234006 and R01CA237569, OHSU Knight Cancer Institute, and Friends of Doernbecher. Support was also received from the College of Pharmacy at Oregon State University, Pap{\'e} Family Pediatric Research Institute at Oregon Health & Science University, and ARCS Scholarship (The Karen Irons Medicis Memorial Scholar Award, Diane and Dick Alexander). The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the manuscript; and in the decision to submit the article for publication. The electron microscopy was performed using the Multiscale Microscopy Core (MMC) at Oregon Health & Science University with technical support from the (OHSU)-FEI Living Lab and the Center for Spatial Systems Biomedicine (OCSSB). Publisher Copyright: {\textcopyright} 2022 Wiley-VCH GmbH.",
year = "2022",
month = nov,
day = "3",
doi = "10.1002/smll.202204436",
language = "English (US)",
volume = "18",
journal = "Small",
issn = "1613-6810",
publisher = "Wiley-VCH Verlag",
number = "44",
}