Development of novel antitumor peptidomimetic drugs targeting Drs/SRPX tumor suppressor

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07169
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor therapeutics
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Yukihiro Tambe 滋賀医科大学, 医学部, 助教 (50283560)
• Research Collaborator: INOUE Hirokazu ; KIM Chul-Jang ; TERADO Tokio ; NAKANO Hirofumi
• Project Period (FY): 2016-10-21 – 2019-03-31
• Keywords: 分子標的薬 / 抗腫瘍活性 / ペプチド模倣 / drs/SRPX / sushiモチーフ

Outline of Final Research Achievements

Drs protein is the tumor suppressor gene product that is closely associated with the malignant transformation of human cancers. In this study, we examined the antitumor activity of MI compounds, which are the small molecular compounds that mimic the partial conformation of Drs. Screening with candidate compounds mimicking the Sushi domain of Drs led to the discovery of MI compounds suppressing human cancer cell lines such as pancreatic, colorectal, and bladder cancers at 10-40 micromolar. These compounds exerted antitumor effects through mechanisms such as apoptosis induction and invasion suppression. These results suggest that Drs may be a new molecular target for human cancer therapy.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

近年、抗癌剤の進歩によって癌の治療成績は大幅に改善した。しかし再発や転移の問題、K-ras変異のある膵臓癌などの難治性癌、耐性獲得、抗癌剤の副作用など解決すべき課題は多く、従来とは異なる機構の抗癌剤開発の必要がある。本研究の成果はDrsが癌治療のための新しい分子標的になる可能性を示唆している。また、Sushiドメインを分子模倣することの有効性を見出したことから、他のSushiドメインを有するタンパク質（IL受容体やセレクチンなど）についても同様のアプローチが有効である可能性が示唆された。