Combination therapy of parp inhibitor for overcoming small cell lung cancer drug-resistance
| Project/Area Number |
15K21185
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Respiratory organ internal medicine
Tumor therapeutics
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| 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) |
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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)
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| Co-Investigator(Renkei-kenkyūsha) |
TAKIGAWA NAGIO 川崎医科大学, 医学部, 教授 (60325107)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| 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)
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| 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 |
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| 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.
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Report
(4 results)
Research Products
(1 results)
