RT Journal Article
SR Electronic
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
FD International Institute of Anticancer Research
SP 637
OP 643
DO 10.21873/cgp.20286
VO 18
IS 5
A1 TAKASHI HIGUCHI
A1 KENTARO IGARASHI
A1 NORIO YAMAMOTO
A1 KATSUHIRO HAYASHI
A1 HIROAKI KIMURA
A1 SHINJI MIWA
A1 MICHAEL BOUVET
A1 HIROYUKI TSUCHIYA
A1 ROBERT M. HOFFMAN
YR 2021
UL http://cgp.iiarjournals.org/content/18/5/637.abstract
AB 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.