Patient-derived orthotopic xenograft models for osteosarcoma individualized precision treatment and effective drug discovery

Takashi Higuchi, Kentaro Igarashi, Hiromichi Oshiro, Kentaro Miyake, Norihiko Sugisawa, Norio Yamamoto, Katsuhiro Hayashi, Hiroaki Kimura, Shinji Miwa, Zhenfeng Duan, Francis J. Hornicek, Hiroyuki Tsuchiya, Robert M. Hoffman

Research output: Contribution to journalReview articlepeer-review

Abstract

Osteosarcoma is the most common malignant primary tumor of bone and mainly occurs in young generations. Due to the heterogeneity, rarity, poor response rate to systemic therapy, and metastatic potential of osteosarcoma, individualized precision medicine and novel drug discovery are greatly needed. Toward this goal, we have established the patient-derived orthotopic xenograft (PDOX) mouse model with surgical orthotopic implantation (SOI) for all major cancers. The PDOX models recapitulate human tumors better than subcutaneous-transplanted xenografts including patient-derived xenograft (PDX). Metastasis is observed to a greater extent in PDOX models due to the intact histology and correct-organ tumor micro-environment of the orthotopically implanted tissue. The present report reviews our research group's experience with the osteosarcoma-PDOX model, and the power of the PDOX models to identify effective therapeutics. We have obtained many promising and surprising results using the osteosarcoma-PDOX model for discovering active approved drugs as well as combinations of them, and experimental therapeutics for individual patients. The patient does not need to suffer from the potential drug toxicity and morbidity of ineffective chemotherapies. In an era of growing promise of new treatment and precision medicine, PDOX models offer a unique opportunity to provide specific and individualized therapy and novel therapeutic options for osteosarcoma patients.

Original languageEnglish
Article number31
JournalAnnals of Joint
Volume6
DOIs
Publication statusPublished - 2021 Jul
Externally publishedYes

Keywords

  • Individualized therapy
  • Osteosarcoma
  • Patient-derived orthotopic xenograft (PDOX)
  • Precision medicine

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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