Molecular analysis of EGFR-TKI resistance and development of overcoming drugs
| Project/Area Number |
24300344
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Clinical oncology
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| Research Institution | Japanese Foundation for Cancer Research |
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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)
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| 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
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | がん化学療法 / 分子標的治療 / 併用療法 / EGFR / ALK / 癌 / EGFR-TKI / MET / c-Met |
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| 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.
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.2014
Author(s)
Ryohei Katayama, Luc Friboulet, Sumie Koike, Elizabeth L. Lockerman, Tahsin M. Khan, Justin F. Gainor, A. John Iafrate, Kengo Takeuchi, Makoto Taiji, Yasushi Okuno, Naoya Fujita, Jeffrey A. Engelman, Alice T. Shaw
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Journal Title
Clinical Cancer Research
Volume: 20
Pages: 5686-5696
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer.2014
Author(s)
Friboulet L, Li N, Katayama R, Lee CC, Gainor JF, Crystal AS, Michellys PY, Awad MM, Yanagitani N, Kim S, Pferdekamper AC, Li J, Kasibhatla S, Sun F, Sun X, Hua S, McNamara P, Mahmood S, Lockerman EL, Fujita N, Nishio M, Harris JL, Shaw AT, Engelman JA
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Journal Title
Cancer Discovery
Volume: 4
Pages: 662-673
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] The mERG1a channel modulates skeletal muscle MuRF1, but not MAFbx, expression.2014
Author(s)
Pond AL, Nedele C, Wang WH, Wang X, Walther C, Jaeger C, Bradley KS, Du H, Fujita N, Hockerman GH, Hannon KM.
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Journal Title
Muscle Nerve
Volume: 49
Pages: 378-388
DOI
Related Report
Peer Reviewed
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[Presentation] Patterns of relapse and prognosis after Crizotinib therapy failure in ALK+ Non-small cell lung cancer.2013
Author(s)
Noriko Yanagitani, Hironari Nishizawa, Ryohei Katayama, Hiroshi Kobayashi, Hiroshi Gyoutoku, Takeshi Uenami, Yuichi Tambo, Keita Kudo, Fumiyoshi Ohyanagi, Atsushi Horiike, Hironori Ninomiya, Noriko Motoi, Kengo Takeuchi, Yuichi Ishikawa, Naoya Fujita, Takeshi Horai, Makoto Nishio.
Organizer
15th World Conference on Lung Cancer
Place of Presentation
Sydney, Australia
Related Report
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