2023 Fiscal Year Final Research Report
Exploration of Novel Therapeutic Agents Based on Sheddase Inhibition of the Hepatocarcinoma Susceptibility Gene MICA
Project/Area Number |
19K08412
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53010:Gastroenterology-related
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Research Institution | Chiba Prefectural University of Health Sciences (2021-2023) Chiba University (2019-2020) |
Principal Investigator |
Tawada Akinobu 千葉県立保健医療大学, 健康科学部, 教授 (10596159)
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Co-Investigator(Kenkyū-buntansha) |
荒井 潤 昭和大学, 医学部, 講師 (30766176)
室山 良介 千葉大学, 大学院医学研究院, 助教 (50549459)
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Project Period (FY) |
2019-04-01 – 2024-03-31
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Keywords | 肝細胞癌 / 新規薬剤開発 / がん薬物療法 |
Outline of Final Research Achievements |
Hepatocellular carcinoma (HCC) is one of the most poor prognosis cancers. HCC cell expresses MICA, an innate immune-related molecule, on their cell surface and is eliminated by NK cells through recognition of NKG2D receptors. HCC cell expresses sheddases such as ADAM9 and ADAM10, which cleave and inactivate MICA on the cell surface for their own survival. We planned to explore the candidate inhibitors of these HCC-related MICA sheddases using a large compound library. Arai et al. showed that several retinoids selectively suppress the sheddase activity of ADAM9 and ADAM10. We plan to further investigate these retinoids as new therapeutic drug candidates for HCC.
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Free Research Field |
肝癌治療、がんゲノム医療
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Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌(肝癌)は最も予後不良のがんのひとつである. 最も代表的な肝癌の治療法は外科的切除であるが肝癌の多くは慢性肝炎・肝硬変を背景に発生するため, 切除後の肝臓が充分な機能を保てない場合は外科的切除の適応外となる.そのため外科的切除以外の治療法開発が強く望まれている. 研究分担者の荒井らのグループにより肝癌細胞に対して有効性を有する可能性のある化合物が示された. 学術的貢献として肝癌治療薬の創薬分野に対して候補化合物を提供したことが挙げられる. 今後, 本化合物が前臨床試験, 臨床試験(治験)を経て臨床実用することができれば肝癌患者へ新規治療法の提示となり社会貢献となりうる.
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