Combination Treatment with Sorafenib and Everolimus Regresses a Doxorubicin-resistant Osteosarcoma in a PDOX Mouse Model

Takashi Higuchi, Norihiko Sugisawa, Kentaro Miyake, Hiromichi Oshiro, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Kentaro Igarashi, Zoey Kline, Paige Belt, Sant P. Chawla, Michael Bouvet, Shree Ram Singh, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Background/Aim: Osteosarcoma is a rare but recalcitrant type of bone cancer. To discover an effective therapy for osteosarcoma, we used a patient-derived orthotopic xenograft (PDOX) mouse model. A PDOX mouse model has been established for all major cancer types. Strong synergistic efficacy of sorafenib (SFN) and everolimus (EVL) has been demonstrated in several cancers. In the present study, we examined the efficacy of a SFN and EVL combination on a doxorubicin (DOX)-resistant osteosarcoma PDOX. Materials and Methods: The osteosarcoma PDOX models were randomly divided into five treatment groups, each containing six mice: Control; DOX; SFN; EVL; and a combination of SFN and EVL. Mice were treated for 14 days. To observe the efficacy of these treatments, tumor size and body weight were measured, and histological sections were analyzed. Results: Tumor growth regression was observed only in the mice treated with the combination of SFN-EVL. Histological analysis revealed necrosis with degenerative changes in tumors treated with a combination of SFN-EVL. Conclusion: A SFN-EVL combination could be a novel effective treatment option for osteosarcoma.

Original languageEnglish
Pages (from-to)4781-4786
Number of pages6
JournalAnticancer research
Issue number9
Publication statusPublished - 2019
Externally publishedYes


  • Combination therapy
  • Drug resistance
  • Everolimus
  • Osteosarcoma
  • PDOX
  • Sorafenib
  • Tumor regression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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