Patient-derived xenograft models for rare cancer drug development

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16430
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kojima Yuki 国立研究開発法人国立がん研究センター, 中央病院, 医員 (40577904)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 希少がん / PDX / ドラッグリポジショニング / バイオマーカー

Outline of Final Research Achievements

1: Therapeutic target protein expression analysis and WES and RNAseq were performed using the PDX of cervical gastric-type adenocarcinoma, showing strong expression of HER3, suggesting a potential therapeutic target.
2: Expression of HER2 was assessed by immunostaining using the rare cancer PDX library. CIC-rearranged sarcoma, a refractory rare cancer, showed low HER2 expression and was evaluated for drug efficacy with a HER2-targeted therapeutic (trastuzumab deruxtecan). Efficacy of trastuzumab deruxtecan was shown in the PDX3 strain of CIC-rearranged sarcoma.

Free Research Field

translational research

Academic Significance and Societal Importance of the Research Achievements

希少がんはproof of concept 取得のための前臨床試験を実施する体制が整っていないため、治療開発が乏しいことが大きな課題である。本研究は希少がんである子宮頸部胃型腺がんおよびCIC-rearranged sarcomaのPDXを用いて、治療標的となるバイオマーカーの同定を行い、CIC-rearranged sarcomaについてはin vivoでの薬剤の薬効を検証した。治療抵抗性かつ予後不良である希少がんにおいて新たな治療開発の可能性を示すことができ、学術的にも社会的にも極めて意義深いと考える。