The combination of oral-recombinant methioninase and azacitidine arrests a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft mouse model

Purpose Cancers are methionine (MET) and methylation addicted, causing them to be highly sensitive to MET restriction. The present study determined the efficacy of restricting MET with oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, azacitidine (AZA) on a chemotherapy-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. Methods The osteosarcoma PDOX models were randomized into five treatment groups of six mice: control; doxorubicin (DOX) alone; AZA alone; o-rMETase alone; o-rMETase-AZA combination. Tumor size and body weight were measured during the 14 days of treatment. Results We found that tumor growth was arrested only by the o-rMETase-AZA combination treatment, as tumors with this treatment exhibited tumor necrosis with degenerative change. Conclusion This study suggests that o-rMETase-AZA combination has clinical potential for patients with chemoresistant osteosarcoma.