Targeting FGFR2 C3 variant in FGFR2 amplified gastric cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16767
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: Adachi Yuta 愛知県がんセンター(研究所), がん標的治療TR分野, 主任研究員 (30833842)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: FGFR2 / 分子標的薬耐性

Outline of Final Research Achievements

To verify that FGFR2C3 silencing is effective in vivo model, we attempted to create a doxycycline-induced shRNA for FGFR2-C3 transcript. After some initial difficulties in generating shRNAs, we succeeded in generating shRNAs, and in vitro analysis showed that the addition of doxycycline decreased FGFR2-C3 gene expression and downstream signaling of FGFR2. However, no inhibition of tumor growth was observed in vivo subcutaneous tumor model. Therefore, we attempted to knock down FGFR2-C3 gene by direct injection of in vivo siRNA into subcutaneous tumors, and while inhibition of tumor growth was confirmed, its antitumor effect was not significant compared with growth suppression we confirmed in vitro model.

Free Research Field

分子標的薬耐性

Academic Significance and Societal Importance of the Research Achievements

in vitroで確認できた細胞増殖抑制効果がin vivoで再現されなかった原因として薬剤送達という点が考慮された。またin vivoでの腫瘍微少環境による抵抗性獲得の可能性も十分に考えられ、今後の治療開発を進めるという観点からは妥当性を担保できない可能性が示唆され、in vivoにおける腫瘍増殖抑制効果を示すような、シークエンス及び核酸医薬の媒体を考慮する必要性があると考えられた。