Integrative proteomic analysis of PDX models to develop targeted therapies for recurrent esophageal cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15543
• 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: Higaki Eiji 愛知県がんセンター(研究所), 分子診断TR分野, 研究員 (60896009)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 食道癌 / PDXモデル / 患者由来細胞 / プロテオミクス / 細胞表面タンパク質 / 術前化学療法 / CRISPR-Cas9 / 合成致死

Outline of Final Research Achievements

Nearly half of operable stage II and III esophageal cancer patients develop recurrence. Effective chemotherapy for metastatic esophageal cancer is limited and there is an urgent need to develop innovative therapies. In this study, we will develop patient-derived xenograft (PDX) models of esophageal cancer and a comprehensive multi-omics analysis of PDX tumors will be performed, including cell surfaceome and phosphoproteome analysis that focus on the identification of activated signalling pathways. In addition, a genome-wide functional screening using the CRISPR-Cas9 system will be performed using the esophageal cancer cell lines established in this study. This will help to elucidate the molecular mechanisms of esophageal cancer and identify a set of cell surface molecules as innovative therapeutic targets to overcome esophageal cancer.

Free Research Field

消化器外科学

Academic Significance and Societal Importance of the Research Achievements

本研究において、食道癌PDXにおける細胞表面タンパク質の発現プロファイルや機能スクリーニングから機能的サーフェスオームデータ基盤を構築し、その分子生物学的理解を深めることで、既存研究では俯瞰しえなかった革新的細胞表面タンパク質治療標的群を大規模に開拓できる。腫瘍特異性が高い細胞表面分子が同定されれば、抗体薬物複合体や癌抗原ワクチン、CAR-T療法など、免疫療法の革新につながることが期待される。また、食道癌特異的に発現する分子は、治療標的としてだけでなく、診断、再発・治療効果予測に有用な組織・血液バイオマーカーとしての展開が期待できる。