| Project/Area Number |
25462181
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Respiratory surgery
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| Research Institution | Oita University |
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Principal Investigator |
Sugio Kenji 大分大学, 医学部, 教授 (70235927)
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| Co-Investigator(Kenkyū-buntansha) |
Miyawaki Michiyo 大分大学, 医学部呼吸器・乳腺外科学講座, 講師 (30404388)
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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 |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肺癌 / EGFR / EGFR-TKI / 分子標的 / 耐性 / バイオマーカー / STK11 / 癌の多様性 |
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| Outline of Final Research Achievements |
The purpose of this study is establishment of biomarker based medicine. We analyzed five samples of EGFR-TKI resistant materials, and detected EGFR T790M in two samples and SCLC transformation in one sample. In SCLC transformation cases, the expression of neuroendocrine marker such as NCAM and synaptophysin, was detected in small part of cancer tissue pre-treated by gefitinib, immunohistochemically. These data suggests that resistant mechanism for EGFR-TKI exist in early stage of lung cancer. NGS analysis showed gain of gene copy in 5q, 9p, 14q(AKT1), 17q(ERBB2), 19p, and loss of gene copy in 8q. In mucinous adenocarcinoma of the lung, next generation sequencing analysis showed mutation of LKB1(STK11) and K-RAS. The analysis for copy number variation (CNV) showed copy loss in FGFR3, NOTCH1, AKT1, and LKB1.
In conclusion, cancer heterogeneity such as mutation burden is suggested to be associated with resistant mechanism for molecular targeted therapy.
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