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Combination therapy of parp inhibitor for overcoming small cell lung cancer drug-resistance

Research Project

Project/Area Number 15K21185
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Tumor therapeutics
Research Institution独立行政法人国立病院機構岡山医療センター(臨床研究部) (2016-2017)
National Hospital Organization Nagoya Medical Center (2015)

Principal Investigator

Minami Daisuke  独立行政法人国立病院機構岡山医療センター(臨床研究部), 呼吸器内科, 医師 (80727470)

Co-Investigator(Renkei-kenkyūsha) TAKIGAWA NAGIO  川崎医科大学, 医学部, 教授 (60325107)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords小細胞肺癌 / PARP阻害剤 / PARP阻害剤 / シスプラチン耐性 / Parp阻害剤 / オラパリブ / 肺小細胞癌 / 耐性克服
Outline of Final Research Achievements

To investigate the effect of a combination of olaparib with cisplatin on small cell lung cancer, cisplatin-resistant cell line, SBC-3/CDDP (Cancer Sci.2013;104:78-84), was used. The combination showed a synergistic effect in vitro according to the combination index in SBC-3/CDDP cells, whereas SBC-3 cells exhibited an antagonistic effect. Immunoblotting assay did not reveal that SBC-3/CDDP cells exhibited higher levels of PARP1 than SBC-3 cells. Next-generation DNA sequencer showed several mutations such as BRACA, BCL2L11, AKT, FGFR, NRG1, CCDC6, ATM, NF1, and CHECK2 in SBC-3/CDDP. In a patient with small cell lung cancer, mutations such as MAPK4 and MYCN in recurrent tumor after chemotherapy including cisplatin were found.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (1 results)

All 2017

All Presentation (1 results)

  • [Presentation] PARP阻害薬併用によるシスプラチン耐性小細胞肺癌の克服2017

    • Author(s)
      南大輔
    • Organizer
      第15回 日本臨床腫瘍学会学術集会
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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