Development of a low-invasive diagnostic method for tumor characterization using macrocyclic peptide

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15306
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kanazawa University
• Principal Investigator: Sato Hiroki 金沢大学, ナノ生命科学研究所, 特任助教 (20781173)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HGF / MET

Outline of Final Research Achievements

Aberrant activation of HGF and its receptor MET signaling is well-known to participate in the acquired resistance to molecular targeted drugs. However, current diagnostic approaches to know activation of HGF-MET pathway are insufficient. We recently identified a macrocyclic peptide, HGF-inhibitory peptide-8 (HiP8) which selectively binds to biologically active HGF. In this study, we attempted to specifically detect active HGF in tumor microenvironments for diagnosis by using HiP8. In immunohistochemical staining of active HGF in human cancer tissues using biotinylated HiP8, the HiP8-proved active HGF showed good correlation with staining scores and localization for MET activation, compared to staining of total HGF. Moreover, in tumor-xenograft models using human HGF-knock-in mice, Cu-64-labeled HiP-8 accumulated in xenografts overexpressing HGF at higher levels than those in HGF-negative xenografts.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

本課題によって達成された活性型HGFの選択的検出は、腫瘍組織内のHGF-METシグナルの活性化状態を反映した診断を可能にし、分子標的薬の治療効果を予測するための新たな診断法になる可能性がある。この診断法が実現すれば、「分子標的薬＋MET阻害剤の併用療法」により、従来の化学療法と比較して、高い治療効果が期待できる症例を選定することが可能になる。