Mechanism for EGFR-TKI resistance in lung cancer patients with mutation of epidermal growth factor receptor
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 |
Section | 一般 |
Research Field |
Respiratory surgery
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Research Institution | Oita University |
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)
|
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 |
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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Report
(3 results)
Research Products
(33 results)
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[Journal Article] Pemetrexed-induced scleroderma-like conditions in the lower legs of a patient with non-small cell lung carcinoma.2016
Author(s)
Ishikawa K, Sakai T, Saito- Shono T, Miyawaki M, Osoegawa A, Sugio K, Ono A, Mori H, Nishida H, Yokoyama S, Okamoto O, Fujiwara S, Hatano Y
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Journal Title
J Dermatol
Volume: -
Issue: 9
Pages: 1071-1074
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma.2015
Author(s)
Ohba T, Toyokawa G, Osoegawa A, Hirai F, Yamaguchi M, Taguchi KI, Seto T, Takenoyama M, Ichinose Y, Sugio K.
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Journal Title
Surg Today (2015 Dec 28 Epub ahead of print)
Volume: Epub ahead of print
Related Report
Peer Reviewed / Open Access
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[Journal Article] Regression of thymoma associated with a multilocular thymic cyst: report of a case.2014
Author(s)
Toyokawa G, Taguchi K, Ohba T, Hirai F, Yamaguchi M, Hamatake M, Seto T, Nishiyama K, Shida Y, Sugio K, Ichinose Y
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Journal Title
Surg Today
Volume: 44
Issue: 3
Pages: 577-80
DOI
Related Report
Peer Reviewed
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[Journal Article] Preoperative Concurrent Chemoradiotherapy of S-1/Cisplatin for Stage III Non-Small Cell Lung Cancer.2013
Author(s)
Yamaguchi M, Toyokawa G, Ohba T, Sasaki T, Kometani T, Hamatake M, Hirai F, Taguchi K, Yamanaka T, Seto T, Takenoyama M, Sugio K, Ichinose Y
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Journal Title
Ann Thorac Surg
Volume: 96
Issue: 5
Pages: 1783-1789
DOI
Related Report
Peer Reviewed
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[Presentation] Non-small cell lung cancer with double driver mutations2014
Author(s)
Atushi Osoegawa, Gouji Toyokawa, Taro Ohba, Michiyo Miyawaki, Masafumi Yamaguchi, Kenichi Taguchi, Takashi Seto, Mitsuhiro Takenoyama, Yukito Ichinose, Kenji Sugio
Organizer
AACR-IASLC Joint Conference on The Molecular Origins of Lung Cancer
Place of Presentation
Hard Rock Hotel, USA
Related Report
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[Presentation] Adenocarcinoma non-small-cell lung cancer patients with EGFR mutations to EGFR-TKI : a retrospective multicenter study ( LOGIK1104 )2013
Author(s)
Kenji Sugio,Taro Ohba, Noriyuki Ebi, Noriaki Nakagaki, Daisuke Himeji, Kosuke Kashiwabara, Koji Inoue Hiroshi Wataya, Masayuki Kawasaki, Yukihiro Misumi, Kenichi Taguchi, Kazuki Nabeshima, Junji Kishimoto, Yukito Ichinose
Organizer
15th World Conference on Lung Cancer
Place of Presentation
Sydney convention and Exibition Centre, Australia
Related Report
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