Combination of CDK4/6 and mTOR Inhibitors Suppressed Doxorubicin-resistant Osteosarcoma in a Patient-derived Orthotopic Xenograft Mouse Model: A Translatable Strategy for Recalcitrant Disease

Background: Osteosarcoma is the most frequent malignant bone neoplasm. The efficacy of combination therapy a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and mammalian-target-of-rapamycin (mTOR) was previously reported in several cancer types. In present study, we evaluated palbociclib (CDK inhibitor) everolimus (mTOR on an osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model. Materials Methods: PDOX models were randomized into five treatment groups seven mice each: Group 1, untreated control; group 2, doxorubicin treatment; 3, 4, 5, palbociclib–everolimus treatment. Treatment duration 2 weeks. Results: reduced tumor-volume ratio model compared with control (p=0.018). Everolimus alone also inhibited growth to (p=0.04), but less than combination. Palbociclib ineffective. There no significant body-weight losses any group. Only induced extensive tumor necrosis observed histopathologically. Conclusion: study demonstrated that CDK4/6 mTOR inhibitors can be translatable approach for doxorubicin-resistant clinic.