TY - JOUR T1 - Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 637 LP - 643 DO - 10.21873/cgp.20286 VL - 18 IS - 5 AU - TAKASHI HIGUCHI AU - KENTARO IGARASHI AU - NORIO YAMAMOTO AU - KATSUHIRO HAYASHI AU - HIROAKI KIMURA AU - SHINJI MIWA AU - MICHAEL BOUVET AU - HIROYUKI TSUCHIYA AU - ROBERT M. HOFFMAN Y1 - 2021/09/01 UR - http://cgp.iiarjournals.org/content/18/5/637.abstract N2 - Background/Aim: Osteosarcoma is a recalcitrant heterogenous malignancy. The aim of the present study was to compare a series of multikinase inhibitors (MKIs) for efficacy on two drug-resistant osteosarcoma patient-derived orthotopic xenograft (PDOX) models in order to identify a clinical candidate. Materials and Methods: The two osteosarcoma PDOX models were tested for response to the following MKIs: pazopanib, sunitinib, sorafenib, crizotinib, and regorafenib, in comparison to first-line treatment with cisplatinum and an untreated control. Results: Regorafenib led to regression of osteosarcoma in both PDOXs. Total necrosis was observed pathologically in the regorafenib-treated tumors. Sorafenib arrested growth, without inducing regression, in one osteosarcoma model but not the other, and the other MKIs only slowed tumor growth. Conclusion: The present study demonstrated that regorafenib is much more effective than the other MKIs tested and has clinical potential against recalcitrant osteosarcoma. ER -