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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Project Status |
Completed (Fiscal Year 2013)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | オーダーメード医療 / 大腸がん / セツキシマブ / EGFR / キナーゼ / プロテオーム / バイオマーカー / 接着阻止 / 大腸癌 / タンパク質リン酸化 / 細胞接着阻止 |
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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Report
(3 results)
Research Products
(37 results)
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[Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysisand subsequent verification using selected reaction monitoring and tissue microarrayanalysis2014
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, Tomonaga T.
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Journal Title
Mol Cell Proteomics.
Volume: M113
Issue: 6
Pages: 37093-37093
DOI
Related Report
Peer Reviewed
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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
Related Report
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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] Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation2013
Author(s)
Kuga, T., Nie, H., Kazami, T., Satoh, M., Matsushita, K., Nomura, F., Maeshima, K., Nakayama, Y., Tomonaga, T.
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Journal Title
Oncogenesis
Volume: 3
Issue: 3
Pages: e94-e94
DOI
Related Report
Peer Reviewed
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[Journal Article] A novel mechanism of keratin cytoskeleton organization through casein kinase I alpha and FAM83H in colorectal cancer.2013
Author(s)
Kuga, T., Kume, H., Kawasaki, N., Sato, M., Adachi, J., Shiromizu, T., Hoshino, I., Nishimori, T., Matsubara, H., and Tomonaga T.
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Journal Title
J Cell Sci
Volume: 126
Pages: 4721-31
DOI
Related Report
Peer Reviewed
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[Journal Article] Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase.2013
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
Issue: 20
Pages: 3251-68
DOI
Related Report
Peer Reviewed
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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 Heterochromatin.2013
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,
Issue: 24
Pages: 17871-17883
DOI
Related Report
Peer Reviewed
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[Journal Article] Serum fibrinogen alpha C-chain 5.9 kDa fragment (FIC 5.9) 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, Nomura F
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Journal Title
Proteomics Clin Appl
Volume: (in press)
Issue: 5-6
Pages: 424-431
DOI
Related Report
Peer Reviewed
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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
Related Report
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[Journal Article] A strategy for large-scale phosphoproteomics and SRM-based validation of human breast cancer tissue samples.2012
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, Tomonaga T.
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Journal Title
J Proteome Res.
Volume: 11
Issue: 11
Pages: 5311-5322
DOI
Related Report
Peer Reviewed
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[Presentation] Quantitative Phosphoproteome Analysis of Cultured Stomach Cancer Cell Lines Aimed at Development of Biomarkers for Prediction of Drug Efficacy2013
Author(s)
Hashiguchi K, Muraoka S, Adachi J, Sato M, Kuga T, Watanabe R, Shiromizu T, Hashimoto Y, Nagano M, Kishida M, Tomonaga T
Organizer
Human Proteome Organization (HUPO) 12th Annual World Congress
Place of Presentation
横浜
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