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2022 Fiscal Year Final Research Report

Development of novel nucleic acid compounds for pancreatic cancer which inhibit the invasiveness and metastasis

Research Project

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Project/Area Number 20K08359
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53010:Gastroenterology-related
Research InstitutionKochi University

Principal Investigator

Taniuchi Keisuke  高知大学, 教育研究部医療学系臨床医学部門, 准教授 (50626869)

Co-Investigator(Kenkyū-buntansha) 和田 猛  東京理科大学, 薬学部生命創薬科学科, 教授 (90240548)
Project Period (FY) 2020-04-01 – 2023-03-31
Keywords膵癌 / 核酸化合物 / デリバリーシステム / 核酸治療
Outline of Final Research Achievements

We identified ARHGEF4 and LAMTOR2, which are localized in the lamellipodia of pancreatic cancer cells and involved in the invasiveness and metastasis. Small interfering RNA (siRNA) compounds against ARHGEF4 and LAMTOR2 to which ligands and cationic peptides were added were injected into human pancreatic cancer organoid-implanted mice through the tail vein. As a result, each siRNA compound was delivered to the pancreatic cancer tissue. In the siRNA-administered group targeting ARHGEF4 or LAMTOR2, pancreatic cancer tissue growth was suppressed compared to the control siRNA-administered group and the gemcitabine-administered group. There was no inflammation or disturbance of tissue architecture in the liver, kidney, or lung of the mouse.

Free Research Field

消化器内科学

Academic Significance and Societal Importance of the Research Achievements

k-ras変異などの膵癌細胞の増殖機序に関する基礎研究の論文発表は多い。しかし、同定された標的分子が膵癌創薬に結びついた例はなく、膵癌研究から誕生した分子標的薬は存在しない。研究代表者らは、膵癌の最大の特徴である「豊富な癌間質を伴う癌細胞の浸潤」を抑制することができれば新薬を開発できるのではないかと考えた。
siRNAのデリバリーシステムとして独自に考案・合成し、siRNA化合物を合成した点が本研究の創造的なところである。本研究の核酸化合物が膵癌細胞の浸潤・転移を抑制することを示すことができれば、世界初の膵癌に対する核酸製剤開発に結び付く可能性がある。

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Published: 2024-01-30  

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