Is secondary resistance preventable in the moleculary targeted therapy
| Project/Area Number |
26640110
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor therapeutics
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| Research Institution | National Cancer Center Japan |
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Principal Investigator |
Nishida Toshirou 国立研究開発法人国立がん研究センター, 東病院, 病院長 (40263264)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKAHASHI Tsuyoshi 大阪大学, 医学系研究科, 助教 (50452389)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 抗がん剤耐性 / 二次遺伝子変異 / KIT遺伝子 / 次世代シークエンサー / mRNAアレイ解析 / 次世代シークエンサー（NGS） / SNV / 癌 / 遺伝子 / 薬剤反応 |
|---|
| Outline of Final Research Achievements |
GIST T1 cell line has been incubated with various concentrations of imatinib and generated imatinib-resistant cells with and without secondary mutations. We found the results as follows; 1. Persistent cells had great changes in the transcriptosomes, whereas resistant cells showed great changes in the genetic mutations. 2. Secondary KIT mutations found in resistant cells could not be chased into and detected in parental cells. This was also confirmed using clinical materials. 3. Phylogenetic-tree analysis, in which branch lengths represent evolutionary time measured by VAF increments, indicated that all resistant cell lines had a similar break point time in generating imatinib-resistance.
These results may suggest that, in the cell lines, imatinib-resistant cells may considered to be generated from a crowd which have expression of detoxification and apoptosis-resistance genes, but not from pre-existing parental cells.
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Report
(3 results)
Research Products
(16 results)
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[Journal Article] The GOLD ReGISTry: a Global, Prospective, Observational Registry Collecting Longitudinal Data on Patients with Advanced and Localised Gastrointestinal Stromal Tumours.2015
Author(s)
Barrios CH, Blackstein ME, Blay JY, Casali PG, Chacon M, Gu J, Kang YK, Nishida T, Purkayastha D, Woodman RC, Reichardt P.
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Journal Title
Eur J Cancer.
Volume: 51（16）
Pages: 2423-33
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cyclin-dependent kinase activity correlates with the prognosis of patients with gastrointestinal stromal tumours.2015
Author(s)
Nishida T, Matsushima T, Tsujimoto M, Takahashi T, Kawasaki Y, Nakayama S, Omori T, Yamamura M, Cho H, Hirota S, Ueshima S, Ishihara H.
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Journal Title
Ann Surg Oncol
Volume: 22（11）
Pages: 3565-73
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors.2015
Author(s)
Isosaka M, Niinuma T, Nojima M, Kai M, Yamamoto E, Maruyama R, Nobuoka T, Nishida T, Kanda T, Taguchi T, Hasegawa T, Tokino T, Hirata K, Suzuki H, Shinomura Y
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Journal Title
PLoS One
Volume: 10
Issue: 7
Pages: e0133754-e0133754
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] KIT And PDGFRA Mutations And the Risk of Gastrointestinal Stromal Tumor Recurrence.2015
Author(s)
Joensuu H, Rutkowski P, Nishida T, Steigen S.E, Brabec P, Plank L, Nilsson B, Braconi C, Bordoni A, Magnusson M.K, Sufliarsky J, Federico M, Jonasson J.G, Hostein I, Bringuier P-P, Emile J-F.
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Journal Title
J Clin Oncol 2015;33(6):634-42.
Volume: 33
Pages: 634-642
Related Report
Peer Reviewed
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