Multikinase-Inhibitor Screening in Drug-resistant Osteosarcoma Patient-derived Orthotopic Xenograft Mouse Models Identifies the Clinical Potential of Regorafenib.
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| 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.
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| Authors | Takashi Higuchi, Kentaro Igarashi, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Michael Bouvet, Hiroyuki Tsuchiya, Robert M Hoffman |
| Journal | Cancer genomics & proteomics (Cancer Genomics Proteomics) 2021 Sep-Oct Vol. 18 Issue 5 Pg. 637-643 ISSN: 1790-6245 [Electronic] Greece |
| PMID | 34479916 (Publication Type: Journal Article) |
| Copyright | Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved. |
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