Sorafenib and Palbociclib Combination Regresses a Cisplatinum-resistant Osteosarcoma in a PDOX Mouse Model.

Abstract

BACKGROUND/AIM:

Recurrent osteosarcoma is a recalcitrant disease; therefore, an improved strategy is urgently needed to provide therapy. In order to develop a novel strategy for this disease, our lab has developed a patient-derived orthotopic xenograft (PDOX) mouse model for osteosarcoma. The combination of sorafenib (SFN) and palbociclib (PAL) was shown to be effective of hepatocellular carcinoma. However, whether this combination is efficacious on osteosarcoma has not been reported. The aim of this study was to determine the efficacy of the SFN and PAL combination on a cisplatinum (CDDP)-resistant osteosarcoma PDOX model.

MATERIALS AND METHODS:

Osteosarcoma PDOX models were randomly divided into five treatment groups: untreated-control, CDDP, SFN, PAL and the combination of SFN and PAL.

RESULTS:

Of these agents, the SFN-PAL combination significantly regressed tumor growth, and enhanced tumor necrosis with degenerative changes in the osteosarcoma PDOX.

CONCLUSION:

The SFN-PAL combination is an effective treatment strategy for osteosarcoma and therefore holds promise for clinical efficacy.

• Authors: Takashi Higuchi, Norihiko Sugisawa, Kentaro Miyake, Hiromichi Oshiro, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Sant P Chawla, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M Hoffman
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 8 Pg. 4079-4084 (Aug 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31366491 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Piperazines
• Pyridines
• Doxorubicin
• Sorafenib
• palbociclib
• Cisplatin

Topics

• Animals
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Cell Line, Tumor
• Cisplatin (administration & dosage)
• Disease Models, Animal
• Doxorubicin (administration & dosage)
• Drug Resistance, Neoplasm (genetics)
• Humans
• Mice
• Neoplasm Recurrence, Local (drug therapy, genetics, pathology)
• Osteosarcoma (drug therapy, genetics, pathology)
• Piperazines (administration & dosage)
• Pyridines (administration & dosage)
• Sorafenib (administration & dosage)
• Tumor Burden (drug effects)
• Xenograft Model Antitumor Assays