• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Is secondary resistance preventable in the moleculary targeted therapy

Research Project

Project/Area Number 26640110
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Tumor therapeutics
Research InstitutionNational Cancer Center Japan

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)

Co-Investigator(Renkei-kenkyūsha) TAKAHASHI Tsuyoshi  大阪大学, 医学系研究科, 助教 (50452389)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
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)
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.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2016 2015 2014

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 3 results,  Open Access: 3 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results) Book (1 results)

  • [Journal Article] The standard diagnosis, treatment and follow-up of gastrointestinal stromal tumors based on guidelines.2016

    • Author(s)
      Nishida T, Blay JY, Hirota S, Kitagawa Y, Kang YK.
    • Journal Title

      Gastric Cancer

      Volume: 19 Pages: 3-14

    • NAID

      40020699921

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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.
    • Journal Title

      Eur J Cancer.

      Volume: 51(16) Pages: 2423-33

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [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.
    • Journal Title

      Ann Surg Oncol

      Volume: 22(11) Pages: 3565-73

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Gastrointestinal stromal tumors in Japanese patients with neurofibromatosis type I.2015

    • Author(s)
      Nishida T, Tsujimoto M, Takahashi T, Hirota S, Blay J-V, Wataya-Kaneda M.
    • Journal Title

      J Gastroenterol

      Volume: s00535 Issue: 6 Pages: 1132-6

    • DOI

      10.1007/s00535-015-1132-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [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
    • Journal Title

      PLoS One

      Volume: 10 Issue: 7 Pages: e0133754-e0133754

    • DOI

      10.1371/journal.pone.0133754

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ABL/KIT/PDGFR阻害薬 ~イマチニブ、ニロチニブ、ダサチニブ~2015

    • Author(s)
      西田俊朗、塚崎邦弘
    • Journal Title

      日本臨床

      Volume: 73(2) Pages: 250-55

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 家族性消化管間質腫瘍(Familial Gastrointestinal stromal tumor)2015

    • Author(s)
      西田俊朗、木下敬弘、芝崎秀儒
    • Journal Title

      日本臨床

      Volume: 73(増刊号6) Pages: 103-7

    • Related Report
      2015 Annual Research Report
  • [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.
    • Journal Title

      J Clin Oncol 2015;33(6):634-42.

      Volume: 33 Pages: 634-642

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Key issues in the clinical management of GIST: an expert discussion.2015

    • Author(s)
      Robert G. Maki, Jean-Yves Blay, George D. Demetri, Jonathan A. Fletcher, Heikki Joensuu, Javier Martín-Broto, Toshirou Nishida, Peter Reichardt, Patrick Schöffski, Jonathan C. Trent.
    • Journal Title

      Oncologist

      Volume: 1 Pages: 1-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Follow-up strategies for patients with gastrointestinal stromal tumor treated with or without adjuvant imatinib after surgery.2015

    • Author(s)
      H. Joensuua, J. Martin-Brotob, T. Nishidac, P. Reichardtd, P. Schöffskie, R. G. Maki.
    • Journal Title

      Eur J Cancer

      Volume: 1 Pages: 1-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] GISTにおけるKIT阻害薬に対する耐性機構2015

    • Author(s)
      西田俊朗、木下敬弘、芝崎秀儒
    • Journal Title

      医学のあゆみ

      Volume: 252 Pages: 802-808

    • Related Report
      2014 Research-status Report
  • [Presentation] Genomic and transcriptomic changes in gastrointestinal stromal tumors with acquired resistance to imatinib2015

    • Author(s)
      Nishida Toshirou, Takahashi Tsuyoshi, Katsuya Tsuchihara, Mamoru Kato
    • Organizer
      European Cancer Congress (18th ECCO and 40th ESMO Annual meeting)
    • Place of Presentation
      Vienna, Austria,
    • Year and Date
      2015-09-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Toshirou Nishida2015

    • Author(s)
      Multidisciplinary treatment for primary GIST
    • Organizer
      Seoul International Symposium of Surgical Oncology 2015
    • Place of Presentation
      韓国 ソウル
    • Year and Date
      2015-02-27 – 2015-02-28
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] The mechanism of acquired resistance to imatinib in gastrointestinal stromal tumor (GIST)2014

    • Author(s)
      Toshirou Nishida, Tsuyoshi Takahashi, Kazuya Tsuchihara
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 高リスクGISTに対する完全切除後の治療に関するレジストリ研究(STAR ReGISTry2014

    • Author(s)
      西田俊朗、長 晴彦、尾阪将人、小松嘉人、黒川幸典、土井俊彦、平井敏弘、北川雄光、
    • Organizer
      第52回日本癌治療学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2014-08-28 – 2014-08-30
    • Related Report
      2014 Research-status Report
  • [Book] 消化器外科学レビュー2015-'162015

    • Author(s)
      西田俊朗、木下敬弘
    • Publisher
      総合医学社
    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2017-05-10  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi