| Project/Area Number |
18390386
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Thoracic surgery
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| Research Institution | Aichi Cancer Center Research Institute |
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Principal Investigator |
MITSUDOMI Tetsuya Aichi Cancer Center Research Institute, Molecular Oncology, Researcher (70209807)
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| Co-Investigator(Kenkyū-buntansha) |
YATABE Yasushi Molecular Oncology, 分子腫瘍学部, Researcher (90280809)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,910,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2007: ¥8,710,000 (Direct Cost: ¥6,700,000、Indirect Cost: ¥2,010,000)
Fiscal Year 2006: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | lung caner / molecular targeted therapy / EGFR gene / individalized therapy / acquired resistance / MET遺伝子 / 遺伝子増幅 / 遺伝子変異 / スプライス異常 / 肺がん / LKB1 / 腺癌 / 喫煙 / EGFR / KRAS / Peutz-Jeghers syndrome |
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| Research Abstract |
Patients with pulmonary adenocarcinoma that harbors mutation of the epidermal growth factor receptor(EGFR) gene often exhibit dramatic response to EGFR-tyrosine kinase inhibitors such as gefitinib. However, its role as a predictive factor has not been established. The purpose of the present project was to analyze EGFR and related genes for individulaization of geftinib treatment for lung cancer.
1) Analyses of KRAS, PIK3CA, PTEN and gefitinib sensitivity : Mutations of the KRAS gene and PIK3CA gene were detected in 9 and 2 of 78 tumors, respectively. None of 6 patients with KRAS mutations responded to gefitinib, while 2 of 2 patients with PIK3CA also had EGFR mutations and both of them responded to gefitunb. In tumors with EGFR mutations, high expressors of PIK3CA and PTEN survived for a longer period.
2) Analysis of acquired resistance to gefitinib : Most of patients who initially responded gefitinib become resistant. Fourteen cases that exhibit acquired resistance were analyzed for the secondary mutations of the EGFR gene. Seven of them had T790M mutation. However, we could not find any other novel mutations. About half of the patients with acquired resistance to gefitinib was due to the secondary T790M that can be treated with the irreversible type of EGFR-TKIs of a new generation. In addition, we confirmed that the role of EGFR gene mutations as predictor of EGFR response in various settings. We also analyzed LKB1 gene status in Japanese lung cancer.
Conclusion : These results can be directly translated into clinic to help select appropriate treatment strategy for patients with lung cancer.
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