@article {HIGUCHI637, author = {TAKASHI HIGUCHI and KENTARO IGARASHI and NORIO YAMAMOTO and KATSUHIRO HAYASHI and HIROAKI KIMURA and SHINJI MIWA and MICHAEL BOUVET and HIROYUKI TSUCHIYA and ROBERT M. HOFFMAN}, title = {Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib}, volume = {18}, number = {5}, pages = {637--643}, year = {2021}, doi = {10.21873/cgp.20286}, publisher = {International Institute of Anticancer Research}, abstract = {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.}, issn = {1109-6535}, URL = {https://cgp.iiarjournals.org/content/18/5/637}, eprint = {https://cgp.iiarjournals.org/content/18/5/637.full.pdf}, journal = {Cancer Genomics \& Proteomics} }