New Therapeutic Strategies for EGFR Exon 20 Insertion Mutation-Positive Lung Cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16398
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kindai University
• Principal Investigator: NISHINO MASAYA 近畿大学, 医学部, 助教 (40709664)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: EGFR遺伝子変異陽性肺癌 / エクソン20挿入変異 / 分子標的治療薬

Outline of Final Research Achievements

Lung cancer is the leading cause of cancer death in Japan, and the efficacy of molecular targeted therapy for EGFR mutation-positive lung cancer has long been established. Among these, no effective therapy has been established for EGFR exon 20 insertion mutations. We established exon 20 mutant lung cancer cell models and sought to identify effective molecular targeted therapies against them and to clarify the mechanism of resistance. poziotinib and tarloxotinib were found to be effective against these lung cancer cell models, and resistant secondary mutation induction using ENU We identified EGFR T790M and C797S as resistant secondary mutations by ENU induction. In addition, a novel drug, mobocertinib, was also evaluated and shown to be effective.

Free Research Field

肺癌

Academic Significance and Societal Importance of the Research Achievements

肺がんは全がん腫の中でも増加傾向にあり、本邦においても死亡者数は年間約8万人に上り、がん死亡数の第1位となっている。EGFR遺伝子変異陽性肺がんは全肺がんの約25%（全肺がんの約半数を占める肺腺がんの約5割）に認められると推計され、EGFR変異肺がんのうちの約10%をEGFRエクソン20挿入変異陽性肺癌が占める。このため、概算ではあるが毎年2000人がEGFRエクソン20挿入変異を有する肺がんで死亡していることとなる。しかし上述の通り、EGFRエクソン20挿入変異を有する肺がんに対する有効な分子標的治療薬は確立されておらず、EGFR-TKIによる恩恵を受けられていない患者群である。