Exploratory study of genomic abnormalities and microenvironment of HER2 gastric cancer that confers resistance to anti-HER2 antibody-drug conjugate

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20839
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Kyushu University
• Principal Investigator: Yamaguchi Kyoko 九州大学, 大学病院, 助教 (50896933)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: HER2陽性胃癌 / 抗体薬物複合体 / がんゲノム異常 / 三次リンパ組織

Outline of Final Research Achievements

First, to investigate the relationship between specific genomic alterations and treatment efficacy, we concluded a contract with the Center for Cancer Genomics and Advanced Therapeutics of the National Cancer Center and analyzed the results of comprehensive genomic profiling tests conducted in Japan. The results showed that HER2-positive gastric cancer patients with a specific genomic alteration tended to have a poorer response to anti-HER2 drug conjugate than those without the alteration. We are analyzing the mechanism by which this genetic alteration is involved in drug resistance.
We are also focusing on lymph node-like structures (tertiary lymphoid structure) that form within cancer, and using multiple fluorescent immunostaining and comprehensive genetic analysis techniques, we are evaluating the correlation between the constituent cells of tertiary lymphoid tissues and the therapeutic effect of drugs.

Free Research Field

腫瘍内科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、抗HER2抗体薬物複合体の治療効果を減弱する可能性のある遺伝子異常が存在することが示唆される結果が得られました。今後はより多い症例集団で解析を行うことと、分子生物学実験でこの遺伝子異常の役割をさらに深めていく予定です。本研究成果は、HER2陽性胃癌において抗HER2抗体薬物複合体の治療効果を予測するためのバイオマーカーの開発ならびに、治療抵抗性のメカニズムを明らかにするための一助として期待されます。