Tumor-targeting Salmonella typhimurium A1-R regresses an osteosarcoma in a patient-derived xenograft model resistant to a molecular-targeting drug

Oncotarget. 2017 Jan 31;8(5):8035-8042. doi: 10.18632/oncotarget.14040.

Abstract

Osteosarcoma occurs mostly in children and young adults, who are treated with multiple agents in combination with limb-salvage surgery. However, the overall 5-year survival rate for patients with recurrent or metastatic osteosarcoma is 20-30% which has not improved significantly over 30 years. Refractory patients would benefit from precise individualized therapy. We report here that a patient-derived osteosarcoma growing in a subcutaneous nude-mouse model was regressed by tumor-targeting Salmonella typhimurium A1-R (S. typhimurium A1-R, p<0.001 compared to untreated control). The osteosarcoma was only partially sensitive to the molecular-targeting drug sorafenib, which did not arrest its growth. S. typhimurium A1-R was significantly more effective than sorafenib (P <0.001). S. typhimurium grew in the treated tumors and caused extensive necrosis of the tumor tissue. These data show that S. typhimurium A1-R is powerful therapy for an osteosarcoma patient-derived xenograft model.

Keywords: Salmonella typhimurium A1-R; nude mouse; osteosarcoma; patient-derived xenograft; tumor-targeting.

MeSH terms

  • Adolescent
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Biological Therapy / methods*
  • Bone Neoplasms / microbiology
  • Bone Neoplasms / pathology
  • Bone Neoplasms / therapy*
  • Drug Resistance, Neoplasm*
  • Humans
  • Male
  • Mice, Nude
  • Molecular Targeted Therapy
  • Necrosis
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Osteosarcoma / microbiology
  • Osteosarcoma / pathology
  • Osteosarcoma / therapy*
  • Phenylurea Compounds / pharmacology*
  • Protein Kinase Inhibitors / pharmacology*
  • Salmonella typhimurium / pathogenicity*
  • Sorafenib
  • Time Factors
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Sorafenib