Clarification of mechanism of gastric tumorigenesis based on cancer stratification and development of novel therapeutic strategy

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03726
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Chiba University
• Principal Investigator: Kaneda Atsushi 千葉大学, 大学院医学研究院, 教授 (10313024)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 胃癌 / エピゲノム / Epstein-Barrウイルス

Outline of Final Research Achievements

In this study, clinical gastric cancer specimens and in vitro models were used to stratify gastric cancer cases based on epigenome characteristics. In particular, for gastric cancer subtypes exhibiting hypermethylation such as EBV gastric cancer and MSI gastric cancer, we elucidated the molecular mechanism of carcinogenesis, identified epigenomic changes important for carcinogenesis, and identified the molecular mechanism that induces the epigenome changes. By applying the molecular properties of the gastric cancer subtypes, we identified promising seed compounds with effective anticancer activity and proceeded with the synthesis of new compounds that could target regions with epigenomic aberrations.

Free Research Field

癌エピゲノム

Academic Significance and Societal Importance of the Research Achievements

胃癌は本邦で毎年10万人以上が罹患し約5万人が命を落とす重要疾患であり、その本態としての発癌分子基盤を解明することは予後を改善するための喫緊の課題である。本研究では、臨床胃癌標本および細胞培養実験により、特にEBV胃癌やMSI胃癌と呼ばれるDNA高メチル化を呈する胃癌サブタイプに対して、エピゲノム異常による全く新たな胃発癌分子機構を同定し、またそのエピゲノム異常を誘導する分子機序を同定した。さらに同定した分子特性を応用し、有効な抗がん作用を有する化合物を同定するなど、新たな薬剤治療戦略の基盤を築いた。