Resistance mechanisms to molecular targeted drugs in lung adenocarcinoma

2015 Fiscal Year Final Research Report

• Project/Area Number: 25710015
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Katayama Ryohei 公益財団法人がん研究会, その他部局等, 主任研究員 (60435542)
• Co-Investigator(Renkei-kenkyūsha): NISHIO Makoto 公益財団法人がん研究会, 有明病院・呼吸器内科, 部長 (00281593) ; YANAGITANI Noriko 公益財団法人がん研究会, 有明病院・呼吸器内科, 医長 (60400785) ; KITAZONO Satoru 公益財団法人がん研究会, 有明病院・呼吸器内科, 副医長 (90527863)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 分子標的薬 / 獲得耐性 / 変異 / チロシンキナーゼ阻害薬

Outline of Final Research Achievements

Non-small cell lung cancer (NSCLC) harboring driver oncogene such as EGFR mutation, ALK-, ROS1-, rearrangements are exquisitely sensitive to small molecule tyrosine kinase inhibitors (TKIs). Although most these driver oncogene positive NSCLC marketly respond to the corresponding TKIs, cancers inevitably develop resistance within a few years by the multiple mechanisms. We explored the resistance mechanisms to TKIs using cell line models and the patient derived specimens. As the results, we succeded to identify and reported various TKI resistance mechanisms in ALK, ROS1 or other driver oncogene positive NSCLC, such as multiple secondary mutations in the kinase domain, bypass pathway activation, or P-glycoprotein overexpression mediated resistance. We also found the potential therapeutic strategies to overcome the resistances. Our study potentially could serve as a framework for selecting and prioritizing therapeutic strategy in the clinic.

Free Research Field

腫瘍治療学