2021 Fiscal Year Final Research Report

Development of novel therapeutics that utilize driver oncogene-induced senescence

Research Project

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Project/Area Number	18H02819
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Review Section	Basic Section 53030:Respiratory medicine-related
Research Institution	Nagoya University
Principal Investigator	Sato Mitsuo 名古屋大学, 医学系研究科(保健), 教授 (70467281)
Co-Investigator(Kenkyū-buntansha)	長谷哲成名古屋大学, 医学部附属病院, 助教 (30621635) 湯川博名古屋大学, 未来社会創造機構, 招へい教員 (30634646) 田中一大名古屋大学, 医学部附属病院, 病院助教 (40809810) 芳川豊史名古屋大学, 医学系研究科, 教授 (00452334) 川口晃司名古屋大学, 医学部附属病院, 病院准教授 (10402611) 川井久美名古屋大学, 医学系研究科(保健), 准教授 (50362231) 横井香平名古屋大学, 医学系研究科, 教授 (60378007)
Project Period (FY)	2018-04-01 – 2021-03-31
Keywords	変異KRAS / 細胞老化
Outline of Final Research Achievements	The purpose of this study was to develop a treatment for mutant KRAS based on the phenomenon of oncogene-induced cellular senescence (OIS) that inhibits proliferation. Using an immortalized normal human bronchial epithelial cell line that expresses mutant KRAS under the control, we performed a pooled shRNA library screening. Gene X was identified as a promising target, followed by high-throughput screening with a compound library to identify multiple candidate compounds that inhibit gene X. However, we stopped the project because of difficulty in developing a further assay system to evaluate inhibitory efficacy of identified compound.
Free Research Field	肺癌
Academic Significance and Societal Importance of the Research Achievements	変異KRASは固形癌において最も高頻度なドライバー癌遺伝子である。ドライバー癌遺伝子は癌細胞の増殖や生存に必須とされ、有効な治療標的となる。本課題は、未だ高い効果を示す治療が開発されていない変異KRAS肺癌の治療開発に取り組んだ。成果として治療標的候補遺伝子Xを特定し、同遺伝子の阻害作用を示すコンパウンドも特定した。変異KRAS癌の治療開発に役立つ知見を得たと考える。