@article{68639d09c29843fb920e28f8b0b791d2,
title = "A targeted combinatorial therapy for Ewing's sarcoma",
abstract = "Ewing's sarcoma (EwS) is the second most common bone cancer in children and adolescents. Current chemotherapy regimens are mainly ineffective in patients with relapsed disease and cause long-term effects in survivors. Therefore, we have developed a combinatorial therapy based on a novel drug candidate named ML111 that exhibits selective activity against EwS cells and synergizes with vincristine. To increase the aqueous solubility of hydrophobic ML111, polymeric nanoparticles (ML111-NP) were developed. In vitro data revealed that ML111-NP compromise viability of EwS cells without affecting non-malignant cells. Furthermore, ML111-NP exhibit strong synergistic effects in a combination with vincristine on EwS cells, while this drug pair exhibits antagonistic effects towards normal cells. Finally, animal studies validated that ML111-NP efficiently accumulate in orthotopic EwS xenografts after intravenous injection and provide superior therapeutic outcomes in a combination with vincristine without evident toxicity. These results support the potential of the ML111-based combinatorial therapy for EwS.",
keywords = "Chemotherapy, Combinatorial therapy, Ewing's sarcoma, ML111, Nanoparticle",
author = "Sabei, {Fahad Y.} and Olena Taratula and Albarqi, {Hassan A.} and Al-Fatease, {Adel M.} and Moses, {Abraham S.} and Demessie, {Ananiya A.} and Youngrong Park and Vogel, {Walter K.} and {Esfandiari Nazzaro}, Ellie and Davare, {Monika A.} and Adam Alani and Mark Leid and Oleh Taratula",
note = "Funding Information: This research was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers R01CA237569 and R37CA234006, National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2 TR002370, the Office of Commercialization and Corporate Development and the Technology Transfer Office at Oregon State University and Oregon Health & Science University, Oregon State University, College of Pharmacy, Jazan University and Najran University. The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; 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 research was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers R01CA237569 and R37CA234006 , National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number KL2 TR002370 , the Office of Commercialization and Corporate Development and the Technology Transfer Office at Oregon State University and Oregon Health & Science University, Oregon State University, College of Pharmacy, Jazan University and Najran University . The funding sources had no involvement in study design; in the collection, analysis and interpretation of data; in the writing of the report; 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} 2021 Elsevier Inc.",
year = "2021",
month = oct,
doi = "10.1016/j.nano.2021.102446",
language = "English (US)",
volume = "37",
journal = "Nanomedicine: Nanotechnology, Biology, and Medicine",
issn = "1549-9634",
publisher = "Elsevier Inc.",
}