Elucidation of the interaction between tumor epithelial cells and stromal cells in acquiring resistance to molecular-targeted drugs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K07139
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: FUJISHITA Teruaki 愛知県がんセンター(研究所), がん病態生理学分野, 主任研究員 (50511870)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 大腸がん / がん微小環境 / 治療抵抗性

Outline of Final Research Achievements

Although molecular-targeted therapy has become a standard therapy for many cancer types, solid tumors acquire resistance against the targeted therapy in most cases. In this study, I investigated the possibility that the tumor microenvironment could be a therapeutic target for colorectal cancer that acquired resistance against targeted therapy. Colorectal cancer tissues that acquired mTOR-inhibitor resistance showed elevated levels of cytokines via MAP kinase pathway activation in the stromal cells building the tumor microenvironment. Because the mTOR-inhibitor resistance of colorectal cancer was abolished by suppression of the activated tumor microenvironment using a MEK inhibitor, the tumor microenvironment is considered a clue for overcoming resistance against targeted therapies.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

標的分子の変異やフィードバック経路の活性化などがん細胞が分子標的薬に対して抵抗性を獲得する方法は様々であり、これまでがん細胞そのものにおける抵抗性獲得機序が研究の対象とされて来た。がん微小環境もまた抵抗性獲得に密接に関与していることが本研究により明らかにされたことで、がん細胞だけでなくがん微小環境を標的とした分子標的薬抵抗性がんの新たな治療戦略の開発に貢献するものと期待される。