FGFR1 as a molecular target of squamous cell lung cancer and the mechanism of FGFR inhibitor-resistance

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K18440
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: The University of Tokyo
• Principal Investigator: Amano Yosuke 東京大学, 医学部附属病院, 助教 (50749330)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 肺扁平上皮癌 / 分子標的治療 / 薬剤耐性

Outline of Final Research Achievements

Molecular-targeted therapy has progressed in lung cancer in recent years, and acquired resistance during molecular-targeted therapy has become a major problem. In squamous cell lung cancer, FGFR has been identified as one of the molecular target and clinical trials of FGFR inhibitor are currently in progress. In this project, we analyzed the mechanism of acquired FGFR-inhibitor resistance.
We previously identified a squamous cell lung cancer cell line which is highly sensitive to FGFR inhibitor AZD4547, and established its resistance clone by exposing gradually-increasing concentration of AZD4547. Gene analysis identified a transcription factor that is expressed more in the resistance clone and is related to the change in the characteristics of cancer. Inhibition of this gene by siRNA induced growth inhibition of resistance clone. Therefore, this gene is one of the responsible genes for the resistance to FGFR targeted therapy.

Free Research Field

肺癌