Development of precision medicine for the soft tissue sarcoma using PDOX mouse model

• Project/Area Number: 20K17991
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Kanazawa University
• Principal Investigator: Igarashi Kentaro 金沢大学, 医学系, 協力研究員 (80622860)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 軟部肉腫 / 個別化医療 / PDOXモデル / 薬剤感受性 / 患者由来組織同所性異種移植 / 薬剤感受性試験 / 患者由来腫瘍同所移植モデル

Outline of Research at the Start

本研究においては40年前に開発された抗がん剤による標準治療以外は新規薬剤による治療法が稀少がんであるがゆえに定まっていない軟部肉腫において，患者臨床をより反映してた動物モデルである患者由来腫瘍同所移植モデルを用い，各種薬剤の感受性試験を行うことで実臨床との相関を証明し，軟部肉腫における個別化医療の開発を目指す．

Outline of Final Research Achievements

In this study, we applied our newly developed "clinically relevant animal model," the Patient Derived Orthotopic Xenograft (PDOX) model mouse, to soft tissue sarcoma. We conducted drug sensitivity tests using drugs currently available in clinical practice. In the established seven PDOX models, the drug sensitivity of the standard treatment drug doxorubicin correlated with the therapeutic effect observed in clinical patients, demonstrating the utility of the mouse model. Additionally, in the sensitivity tests using currently available drugs, we identified drugs that showed greater efficacy than doxorubicin.

Academic Significance and Societal Importance of the Research Achievements

軟部肉腫は発生頻度の低い希少がんであり，さまざまな病理型の腫瘍が存在するため患者数の多い癌腫と比較して新規薬剤の有効性を大規模臨床試験で判定することが難しいた．我々が開発した患者臨床をより反映した患者由来組織同所性異種移植を用いた薬剤感受性試験により有効な薬剤を見出すことは軟部肉腫の個別化医療の開発につながる重要な一歩であると考える．

Research Products

• [Presentation] Newly developed bone targeting platinum complex effectively targets cisplatin resistant relapsed osteosarcoma in a patientderived orthotopic xenograft (PDOX) model (2023)
  • Author(s): Igarashi K, Yamamoto N, Hayashi K, Takeuchi A, Miwa S, Higuchi T, Taniguchi Y, Morinaga S, Asano Y , Hoffman RM, Tsuchiya H
  • Organizer: Annual meeting of the American academy of othropaedic surgeons
  • Int'l Joint Research
• [Presentation] Patterns of sensitivity to a panel of drugs are highly individualized for undifferentiated/unclassified soft tissue sarcoma (USTS) in patient-derived orthotopic xenograft (PDOX) nude-mouse models (2022)
  • Author(s): Igarashi K 1 , Yamamoto N 1 , Hayashi K 1 , Takeuchi A 1 , Miwa S 1 , Higuchi T 1 , Taniguchi Y 1 , Morinaga S 1 , Asano Y 1 , Hoffman R 2 , Tsuchiya H 1 1 Orthopaedic surgery, Kanazawa University, Kanazawa Ishikawa, Japan 2 Department of Surgery, University of California San Diego, San Diego California, USA
  • Organizer: International society of limb salvage
  • Int'l Joint Research
• [Presentation] Tumor-targeting Salmonella typhimurium A1-R is an effective general therapeutic for undifferentiated/unclassified soft tissue sarcoma (USTS) patient-derived orthotopic xenograft(PDOX) nude-mouse model (2022)
  • Author(s): Igarashi K 1 , Yamamoto N 1 , Hayashi K 1 , Takeuchi A 1 , Miwa S 1 , Higuchi T 1 , Taniguchi Y 1 , Morinaga S 1 , Asano Y 1 , Hoffman R 2 , Tsuchiya H 1 1 Orthopaedic surgery, Kanazawa University, Kanazawa Ishikawa, Japan 2 Department of Surgery, University of California San Diego, San Diego California, USA
  • Organizer: International society of limb salvage
  • Int'l Joint Research