PT  - JOURNAL ARTICLE
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
TI  - Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib
AID  - 10.21873/cgp.20286
DP  - 2021 Sep 01
TA  - Cancer Genomics - Proteomics
PG  - 637--643
VI  - 18
IP  - 5
4099  - http://cgp.iiarjournals.org/content/18/5/637.short
4100  - http://cgp.iiarjournals.org/content/18/5/637.full
SO  - Cancer Genomics Proteomics2021 Sep 01; 18
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.