Simultaneous development of novel treatment and companion biomarker of colorectal cancer based on CTOS method

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07926
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyoto University
• Principal Investigator: Jumpei Kondo 京都大学, 医学研究科, 特定助教 (80624593)
• Co-Investigator(Kenkyū-buntansha): 井上 正宏 京都大学, 医学研究科, 特定教授 (10342990)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 大腸癌 / オルガノイド / 薬剤感受性 / バイオマーカー / 多様性

Outline of Final Research Achievements

Drug sensitivity assay using colorectal CTOS suggested that BMP inhibitor is a candidate for a novel drug in a portion of colorectal cancer cases. Constitutive inactivation of BMP/SMAD pathway as well as lack of autocrine BMP ligands might be the cause of insufficient effect of BMP inhibitor. BMP inhibition suppressed MEK/ERK pathway in sensitive cases. Combination effect was observed with MEK inhibitor, but not with cetuximab, both in vitro and in vivo xenograft experiments. In vitro sensitivity assay results, which well correlated with in vivo effect of BMP/MEK inhibition is suggested to be a potential functional biomarker.

Free Research Field

消化器内科

Academic Significance and Societal Importance of the Research Achievements

CTOSを用いた薬剤感受性アッセイ、移植腫瘍治療などにより、新規治療法の候補が導出された。またIn vitroでのCTOSを用いた感受性アッセイは、機能的バイオマーカーとして有用な可能性が示唆された。さらに、併用効果をもたらす分子機序およびバイオマーカー開発に向け、取得したデータの解析を継続することで、より有効な治療法や患者選択に繋がると期待される。