2013 Fiscal Year Final Research Report
Discovery of protein phosphorylation markers to predict the efficacy of anti-EGFR antibody drugs in colorectal cancer patients
Project/Area Number |
24790184
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Medical pharmacy
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Research Institution | 独立行政法人医薬基盤研究所 |
Principal Investigator |
KUGA Takahisa 独立行政法人医薬基盤研究所, 創薬基盤研究部, 研究員 (20551857)
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Research Collaborator |
TOMONAGA Takeshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (80227644)
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Project Period (FY) |
2012-04-01 – 2014-03-31
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Keywords | オーダーメード医療 |
Research Abstract |
Anti-EGFR antibody drugs have been approved for metastatic colorectal cancer (mCRC) therapy, but the drugs are ineffective for CRC exhibiting EGF-independent activation of the EGFR signaling pathway. Although a part of the patients with the aberrant EGFR signaling can be detected by the KRAS mutation testing, further improvement of the method detecting the EGFR signaling-aberrant patients is needed. In this study, using colorectal cancer cell lines, we examined whether comprehensive analysis of activation levels of kinases related to the EGFR signaling could potentiate to predict the efficacy of the anti-EGFR drugs. In addition, I found a novel mechanism by which the anti-EGFR drugs inhibit proliferation of CRC cells. This study showed several biomarker candidates to predict the efficiency of the anti-EGFR antibody drugs.
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[Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring and tissue microarray analysis2014
Author(s)
Kume H., Muraoka S., Kuga T., Adachi J., Narumi R., Watanabe S., Kuwano M., Kodera Y., Matsushita K., Fukuoka J., Masuda T., Ishihama Y., Matsubara H., Nomura F., and Tomonaga T
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Journal Title
Mol Cell Proteomics
Volume: (in press)
DOI
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[Journal Article] Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase2013
Author(s)
Aoyama K., Yuki R., Horiike Y., Kubota S., Yamaguchi N., Morii M., Ishibashi K., Nakayama Y., Kuga T., Hashimoto Y., Tomonaga T., and Yamaguchi N.
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Journal Title
Exp Cell Res
Volume: 319
Pages: 3251-3268
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[Journal Article] Phosphorylation of KRAB-associated Protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by Nuclear Tyrosine Kinases Inhibits the Association of KAP1 and Heterochromatin Protein 1alpha (HP1alpha) with Heterochromatin2013
Author(s)
Kubota S., Fukumoto Y., Aoyama K., Ishibashi K., Yuki R., Morinaga T., Honda T., Yamaguchi N., Hashimoto Y., Kuga T., Tomonaga T., and Yamaguchi N.
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Journal Title
J Biol Chem
Volume: 288
Pages: 17871-17883
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[Journal Article] Serum fibrinogen alpha C-chain 5.9 kDa fragment as a biomarker for early detection of hepatic fibrosis related to hepatitis C virus2013
Author(s)
Sogawa K., Noda K., Umemura H., Seimiya M., Kuga T., Tomonaga T., Nishimura M., Kanai F., Imazeki F., Takizawa H., Yoneda M., Nakajima A., Tsutsumi M., Yokosuka O., and Nomura F.
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Journal Title
Proteomics Clin Appl
Volume: 7
Pages: 424-431
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[Journal Article] A strategy for large-scale phosphoproteomics and SRM-based validation of human breast cancer tissue samples2012
Author(s)
Narumi R., Murakami T., Kuga T., Adachi J., Shiromizu T., Muraoka S., Kume H., Kodera Y., Matsumoto M., Nakayama K., Miyamoto Y., Ishitobi M., Inaji H., Kato K., and Tomonaga T.
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Journal Title
J Proteome Res
Volume: 11
Pages: 5311-5322
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