Molecular analysis of EGFR-TKI resistance and development of overcoming drugs

2014 Fiscal Year Final Research Report

• Project/Area Number: 24300344
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: FUJITA Naoya 公益財団法人がん研究会, がん化学療法センター, 所長 (20280951)
• Research Collaborator: SATO Shigeo ; KATAYAMA Ryohei ; OH-HARA Tomoko ; TAKAMI Miho ; KOIKE Sumie ; NODA Sachie ; AOYAMA Aki ; MIYATA Kenichi ; KOBAYASHI Yuka ; SAKASHITA Takuya ; HIRAIAWA Yukari ; TAKATORI Kazuki ; FUSE Miho Jane
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: がん化学療法 / 分子標的治療 / 併用療法 / EGFR / ALK

Outline of Final Research Achievements

In this project, we tried to analyze the mechanisms of EGFR-TKI and ALK-TKI resistance and to develop overcoming drugs. We performed the following experiments and obtained several new findings.
(1) We searched the EGFR binding protein and found that Aki1, a scaffold protein, interacted with EGFR and mediated EGFR-TKI resistance. We could not find out the positive relationship between Pim kinase expression and EGFR-TKI resistance. During the analysis of c-met signaling pathway for EGFR-TKI resistance, we found that a c-met inhibitor tivantinib, exhibited anti-tumor activity by inhibiting tubulin polymerization.
(2) Using patient-derived samples, we succeeded to identify several mutations that were associated with ALK-TKI resistance. Theese resistance could be overcame the second generation ALK-TKIs, such as alectinib and ceritinib.

Free Research Field

がん化学療法学