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A targeted combinatorial therapy for Ewing's sarcoma

Fahad Y Sabei1, Olena Taratula2, Hassan A Albarqi3

  • 1Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, OR, USA; Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.

Nanomedicine : Nanotechnology, Biology, and Medicine
|July 25, 2021
PubMed

Insights

A new therapy combining ML111 nanoparticles and vincristine shows promise for treating relapsed Ewing sarcoma (EwS) in children and adolescents. This approach targets cancer cells effectively with minimal toxicity to healthy cells.

Area of Science:

  • Pediatric Oncology
  • Nanomedicine
  • Drug Development

Background:

  • Ewing sarcoma (EwS) is a prevalent pediatric bone cancer with limited treatment options for relapsed cases.
  • Current chemotherapy for EwS can be ineffective in recurrent disease and leads to significant long-term side effects in survivors.

Purpose of the Study:

  • To develop a novel combinatorial therapy for EwS using a new drug candidate, ML111, and vincristine.
  • To enhance the delivery and efficacy of ML111 through polymeric nanoparticle formulation (ML111-NP).

Main Methods:

  • Formulation of hydrophobic ML111 into aqueous-soluble polymeric nanoparticles (ML111-NP).
  • In vitro evaluation of ML111-NP and ML111-NP plus vincristine combination on EwS and non-malignant cells.
  • In vivo assessment of ML111-NP accumulation and therapeutic efficacy in orthotopic EwS xenograft models.

Main Results:

  • ML111-NP demonstrated selective toxicity towards EwS cells, sparing non-malignant cells.
  • The combination of ML111-NP and vincristine showed synergistic anti-cancer effects on EwS cells but not on normal cells.
  • Intravenously administered ML111-NP effectively accumulated in EwS tumors, leading to superior therapeutic outcomes with vincristine without observable toxicity.

Conclusions:

  • ML111-NP in combination with vincristine represents a promising therapeutic strategy for relapsed Ewing sarcoma.
  • This combinatorial approach offers targeted efficacy and a favorable safety profile, addressing unmet needs in EwS treatment.
Keywords:
ChemotherapyCombinatorial therapyEwing's sarcomaML111Nanoparticle

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