@techreport{oai:kindai.repo.nii.ac.jp:00021505, author = {田中, 薫}, month = {}, note = {https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17K15032/, 研究成果の概要(和文):本研究には16例のALK-TKIに耐性を獲得したEML4-ALK融合遺伝子陽性肺癌患者を登録。全例で耐性後に血液検体採取し、12例では耐性後に再生検を施行し組織採取ができた。10例で治療前後両方の腫瘍組織検体を集めており、収集した検体から抽出したDNAを用いて行った体細胞遺伝子変異解析から5つの既知のALK遺伝子の2次変異を検出した。2次耐性変異検出例の患者背景としては、男性、非喫煙又は軽喫煙者が多く、全例Alectinibの投与歴を有していた。2次耐性変異検出例では全例で後治療が施行されており、4例で第3世代ALK-TKIであるLorlatinibが投与され、全例で腫瘍縮小効果が得られた。研究成果の概要(英文):Between November 2016 and May 2019, 16 EML4-ALK fusion gene-positive patients were enrolled following disease progression on first- or second-generation ALK inhibitors. Blood samples were collected in all patients, and re-biopsy was performed in 12 patients. Paired samples of pre- and post-ALK-TKI treatment were collected in 10 patients and next-generation sequencing was performed. Among the 12 patients undergoing ALK-TKI-resistant biopsies, 6 (50.0%) had secondary mutations. The most common ALK resistance mutation was G1202R (2 cases), and the remaining ALK resistance mutations included: G1269A, L1196M, V1180L, and F1174L. The characteristics of patients with secondary mutations were mostly males (83.3%), non-smokers (50%), or light smokers (33.3%), and all patients pretreated with alectinib. Of the 4 patients (66.7%) with secondary mutations were treated with lorlatinib, a third-generation ALK-TKI, and all patients had a response to lorlatinib., 研究種目:若手研究(B); 研究期間:2017~2019; 課題番号:17K15032; 研究分野:臨床腫瘍学; 科研費の分科・細目:, application/pdf}, title = {ALK融合遺伝子陽性非小細胞肺癌におけるALK-TKI耐性機序に関する研究}, year = {2020}, yomi = {タナカ, カオル} }