Takashi Higuchi1,2,3, Kentaro Igarashi3, Norio Yamamoto3, Katsuhiro Hayashi3, Hiroaki Kimura3, Shinji Miwa3, Michael Bouvet2, Hiroyuki Tsuchiya4, Robert M Hoffman5,2. 1. AntiCancer, Inc., San Diego, CA, U.S.A. 2. Department of Surgery, University of California, San Diego, CA, U.S.A. 3. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. 4. Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan all@anticancer.com tsuchi@med.kanazawa-u.ac.jp. 5. AntiCancer, Inc., San Diego, CA, U.S.A.; all@anticancer.com tsuchi@med.kanazawa-u.ac.jp.
Abstract
BACKGROUND/AIM: Recurrent osteosarcoma is recalcitrant with poor response rates to first-line chemotherapy due to heterogeneity and metastatic potential. This disease requires novel drug discovery and precision treatment. MATERIALS AND METHODS: The osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model mimics the clinical disease and has identified effective clinically-approved drugs and experimental agents, especially drug combinations, that hold much clinical promise. RESULTS: Effective treatment for drug-resistant osteosarcoma includes regorafenib, as monotherapy, and temozolomide-irinotecan, trabectedin-irinotecan, sorafenib-everolimus, sorafenib-palbociclib, and olaratumab-doxorubicin-cisplatinum, as combinations. CONCLUSION: The PDOX model can be used to improve the outcome of osteosarcoma patients, including individualized, precision therapy.
BACKGROUND/AIM: Recurrent osteosarcoma is recalcitrant with poor response rates to first-line chemotherapy due to heterogeneity and metastatic potential. This disease requires novel drug discovery and precision treatment. MATERIALS AND METHODS: The osteosarcoma patient-derived orthotopic xenograft (PDOX) mouse model mimics the clinical disease and has identified effective clinically-approved drugs and experimental agents, especially drug combinations, that hold much clinical promise. RESULTS: Effective treatment for drug-resistant osteosarcoma includes regorafenib, as monotherapy, and temozolomide-irinotecan, trabectedin-irinotecan, sorafenib-everolimus, sorafenib-palbociclib, and olaratumab-doxorubicin-cisplatinum, as combinations. CONCLUSION: The PDOX model can be used to improve the outcome of osteosarcoma patients, including individualized, precision therapy.