Development of new therapeutic strategies for driver mutation-positive lung cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08601
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Kyoto University
• Principal Investigator: Ozasa Hiroaki 京都大学, 医学研究科, 助教 (80572015)
• Co-Investigator(Kenkyū-buntansha): 青木 航 京都大学, 農学研究科, 助教 (10722184) ; 吉田 博徳 京都大学, 医学研究科, 特定病院助教 (60839710)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肺癌 / YAP1 / 治療初期生存 / ドライバー遺伝子 / 分子標的治療薬

Outline of Final Research Achievements

Molecular-targeted therapies for driver oncogenes have dramatically improved the prognosis of advanced non-small cell lung cancer.　However, it has become a clinical problem that some of the cancer cells survive and grow again. In this study, we discovered that YAP-1 played an important role in the survival mechanism of some cancer cells exposed to molecular-targeted drugs. When driver oncogenes-positive lung cancer cells were exposed to molecular-targeted drugs suitable for each, activation of YAP-1 could maintain cell survival signals in the cancer cells. The combination therapy with YAP1 inhibitor and molecular-targeted drug could suppress tumor regrowth in vivo.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

ドライバー変異陽性肺癌において、YAP1を阻害する薬剤と分子標的治療薬の併用は、治療初期の段階でがん細胞をより多く死滅させることにより、再増大までの期間を延長させることができる可能性が示唆されました。この結果は、肺がんの予後を改善に寄与するとともに、肺がんの根治を目指した新規治療戦略の礎になる可能性があります。今後は、臨床応用できるYAP1阻害剤の開発を進めていく必要があります。