Development of novel therapeutics strategies for lung cancer harboring BRAF non-V600E mutations

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55040:Respiratory surgery-related
• Research Institution: Kawasaki Medical School
• Principal Investigator: Yukawa Takuro 川崎医科大学, 医学部, 講師 (80388975)
• Co-Investigator(Kenkyū-buntansha): 猶本 良夫 川崎医科大学, 医学部, 教授 (00237190) ; 深澤 拓也 川崎医科大学, 医学部, 准教授 (20379845)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 肺癌 / 分子標的療法 / BRAF

Outline of Final Research Achievements

BRAF is an important driver gene for lung cancer, as are EGFR, ALK, ROS1fusion, and RET fusion. The most common BRAF mutation is V600E (41%), but other non-V600E mutations such as K601E, D594G, and G469A are also frequently detected. Non-V600E mutations can be further classified into an intermediate type that forms a dimer with wild-type BRAF and can activate downstream signals, and an impaired type that forms a dimer with wild-type CRAF and induces weak activity.
The results of our study indicated that BRAF inhibitors in combination with MEK inhibitors and EGFR inhibitors may induce a high tumor effect in lung adenocarcinomas with the above non-V600E mutation.

Free Research Field

呼吸器外科学

Academic Significance and Societal Importance of the Research Achievements

バイオマーカーに基づいた患者選択いわゆるPrecision Medicine が現実化し、EGFR変異、ALK転座、ROS1転座およびBRAF変異に対する分子標的薬は、肺癌患者の予後を着実に延長している。BRAF変異は多種の癌に認められるが、有効な治療法開発はこれまでV600E変異を中心に進められてきた。これまでの研究成果から、肺癌は他の癌に比べnon-V600E変異が多く認められることが示されている。本研究は、活性中間型、そして不活型non-V600E変異を持つ肺癌に対する新規治療法開発の糸口を提示しており、その学術的意義は大きい。