Developing a novel therapeutic strategy for advanced gastric cancer using the new genetic pathway of HIF-1 alpha.

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K17439
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Sapporo Medical University
• Principal Investigator: Osuga Takahiro 札幌医科大学, 医学部, 助教 (40619714)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 胃癌 / HIF-1α

Outline of Final Research Achievements

In this study, we succeeded in culturing gastric cancer cells in a low oxygen state, and found that the number of tumor cells decreased in the low oxygen state compared to the normal oxygen state. Regarding the role of REL in hypoxia in gastric cancer, its inhibition alone could not inhibit the tumor's resistance to hypoxia. This may be due to the activation of other gene pathways by inhibiting REL, resulting in resistance to hypoxia. It was considered to be an important finding because it differs from previous studies on colorectal cancer. In addition, histological and clinical studies have revealed the characteristics of gastric cancer that occurs in smokers. Since there is a slight tendency in the relationship between smoking and HIF-1α, we plan to conduct positive histological analysis and patient background statistical analysis in the future.

Free Research Field

悪性腫瘍

Academic Significance and Societal Importance of the Research Achievements

ヘリコバクターピロリ除菌時代における胃癌の原因として喫煙が注目されている。肺癌においてタバコ抽出物の暴露によるHIF-1αの活性化が示されている。そこで本研究では、喫煙者の胃癌の特徴をHIF-1αを通して検討し、HIF-1αの下流遺伝子で、大腸癌で発癌と関係する可能性があるRELを標的とした胃癌治療が可能か検討した。その結果、RELの阻害剤のみでは腫瘍細胞の低酸素での耐性を解除することができず、大腸癌と異なった遺伝子機構の存在が示唆された。組織学的な検討では、喫煙者ではややHIF-1α活性化が多い傾向であり、これらの知見は今後のHIF-1αを標的とした胃癌治療の開発で役立つと考えられた。