A targeted combinatorial therapy for Ewing's sarcoma

Fahad Y. Sabei, Olena Taratula, Hassan A. Albarqi, Adel M. Al-Fatease, Abraham S. Moses, Ananiya A. Demessie, Youngrong Park, Walter K. Vogel, Ellie Esfandiari Nazzaro, Monika A. Davare, Adam Alani, Mark Leid, Oleh Taratula

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish (US)
Article number102446
JournalNanomedicine: Nanotechnology, Biology, and Medicine
StatePublished - Oct 2021


  • Chemotherapy
  • Combinatorial therapy
  • Ewing's sarcoma
  • ML111
  • Nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science


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