Mechanisms of Resistance to Conventional Therapies for Osteosarcoma

Osteosarcoma is the most common primary bone tumor representing approximately 30% of bone sarcomas, and mainly affecting children and adolescents with an 18-years incidence peak

Louise Marchandet; Morgane Lallier; Céline Charrier; Marc Baud’huin; Benjamin Ory; François Lamoureux

2021

Scholarcy highlights

  • Osteosarcoma is the most common primary bone tumor representing approximately 30% of bone sarcomas, and mainly affecting children and adolescents with an 18-years incidence peak
  • It is well described that OS originates from mesenchymal stem cells or osteoblasts and can be divided into different subtypes that are osteoblastic, chondroblastic, and fibroblastic
  • A study showed that cancer stem cells cell line, 3AB-OS, selected from human OS MG-63 cells by long-term treatment with 3-aminobenzamide, were positive for a pluripotent stem cell marker, CD133 and exhibited higher expression of the ATP-binding cassette subfamily G member 2 transporter gene involved in drug efflux, as well as higher expression of anti-apoptotic genes, including Bcl-2, leading to resistance
  • An increased expression of drug efflux transporters P-gp and BCRP/ABCG2 in a population of OS CSCs derived from the HOS-MNNG cell line has been shown, suggesting that stem cells play a role in chemotherapy resistance of tumors
  • Trabectedin, a chemotherapeutic agent that binds to DNA and causes damage and apoptosis, showed no effect when used as monotherapy, while the use of Trabectedin combined with conventional chemotherapy agents could be beneficial and suppress resistance-associated genes
  • If this rate is less than 90%, the patient is a bad responder
  • This technology consists of grafting a cytotoxic agent onto a monoclonal antibody, which is able to bind an antigen on the surface of cancer cells

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