Development of G-quadruplex ligands that target cancer stem cells
Project/Area Number |
25290060
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Tumor therapeutics
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Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
Seimiya Hiroyuki 公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 部長 (50280623)
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Co-Investigator(Renkei-kenkyūsha) |
NAGASAWA Kazuo 東京農工大学, 大学院工学研究院生命工学専攻生命有機化学講座, 教授 (10247223)
MATSUSAKA Satoshi 公益財団法人がん研究会, がん研有明病院消化器化学療法科, 医長 (00372665)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
|
Keywords | がん幹細胞 / テロメア / 分子標的 / DNA損傷 / グアニン4重鎖 / 神経膠腫 / 複製 / 創薬 / G4リガンド |
Outline of Final Research Achievements |
This study aims to develop G4 ligands that stabilize G-quadruplex (G4), a specialized structure of nucleic acids, and establish their anti-proliferative effects on cancer stem cells and the underlying molecular mechanisms. We found that G4 ligands, such as telomestatin and its derivative, X, preferentially attack the cancer stem cells of intractable glioblastoma (GSC). Our observations suggest that single-stranded DNA formed during replication and transcription causes G4 formation, which is targeted by G4 ligands. As a molecular mechanism that could explain the higher sensitivity of GSCs to G4 ligands, GSCs exhibited excessive response to the drug-induced replication stress. X inhibited the growth of GSC-derived tumors explanted in mice. These observations are fundamental achievement for development of G4 ligands as anticancer drugs.
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Report
(4 results)
Research Products
(47 results)
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[Journal Article] Report on the use of nonclinical studies in the regulatory evaluation of oncology drugs2016
Author(s)
Hayakawa Y, Kawada M, Nishikawa H, Ochiya T, Saya H, Seimiya H, Yao Y, Hayashi M, Kai C, Matsuda A, Naoe T, Ohtsu A, Okazaki T, Saji H, Sata M, Sugimura H, Sugiyama Y, Toi M, Irimura T
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Journal Title
Cancer Sci
Volume: 107(2)
Issue: 2
Pages: 189-202
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation2015
Author(s)
Mashima T, Ushijima M, Matsuura M, Tsukahara S, Kunimasa K, Furuno A, Saito S, Kitamura M, Soma-Nagae T, Seimiya H, Dan S, Yamori T, Tomida A
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Journal Title
Cancer Science
Volume: in press
Issue: 7
Pages: 909-920
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of ATP citrate lyase induces an anticancer effect via reactive oxygen species: AMPK as a predictive biomarker for therapeutic impact2013
Author(s)
Migita, T., Okabe, S., Ikeda, K., Igarashi, S., Sugawara, S., Tomida, A., Taguchi, R., Soga, T., Seimiya, H.
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Journal Title
Am J Pathol.
Volume: 182
Issue: 5
Pages: 1800-1810
DOI
Related Report
Peer Reviewed
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