| Project/Area Number |
18H02870
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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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| Review Section |
Basic Section 55010:General surgery and pediatric surgery-related
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| Research Institution | Osaka University |
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Principal Investigator |
Kim Seung Jin 大阪大学, 医学系研究科, 招へい准教授 (90346213)
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| Co-Investigator(Kenkyū-buntansha) |
下田 雅史 大阪大学, 医学系研究科, 講師 (30644455)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2018: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
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| Keywords | エクソーム解析 / 乳癌 / 術前化学療法 / HRD / 感受性 / 予後 / 全エクソーム解析 / 抗癌剤感受性 |
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| Outline of Final Research Achievements |
This study conducted whole exome sequencing analysis of somatic and germline DNAs from biopsied tumor samples and their peripheral blood leukocytes (PBL), respectively, in 120 breast cancer patients treated with neoadjuvant chemotherapy in order to evaluate the predictive factors. Of 120 tumors, 30 were determined to be homologous repair deficiency (HRD)-high tumors, which had significantly higher pCR rates (39% vs. 10%, P = 0.003). When using a combination analysis of HRD and TIL, the pCR rates were different according to subgroups as follows: HRD-high/TIL-high 56%, high/low 29%, low/high 18%, and low/low 6%. This study showed that the HRD might be predictive for neoadjuvant paclitaxel - FEC therapy using alone as well as a combination with TIL.
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| Academic Significance and Societal Importance of the Research Achievements |
遺伝子損傷修復機構の破綻(Homologous Recombination Deficiency, HRD) はがん化だけでなく、PARP阻害剤やプラチナ系抗癌剤の感受性にも関与する。乳癌では特にトリプルネガティブにおいて、HRDは感受性因子になることが報告されている。しかし、本研究はゲノム情報から求めたHRDが、最も汎用されている抗癌剤治療であるタキサン系-アンスラサイクリン系抗癌剤の感受性を、しかも乳癌では最も頻度の高いサブタイプであり抗癌剤感受性の低いルミナル乳癌において予測可能であること示した。本結果は、実臨床の場で多くの乳癌患者に応用できることが期待できる。
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