2020 Fiscal Year Final Research Report
Comprehensive Analysis of Molecular Characteristics of Extramammary Pagets disease
| Project/Area Number |
19K16843
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kindai University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | パジェット病 / Estrogen receptor / Progesterone receptor / HER2 / 網羅的遺伝子発現解析 |
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| Outline of Final Research Achievements |
AAAWe analyzed 20 patients with metastatic or recurrent extramammary Paget’s disease (EMPD). Protein expressions and gene expression analysis were performed, and we evaluated the relationship between the tumor profile and the treatment outcome and the survival. HER2 gene alteration was observed in a fraction of patients with EMPD, furthermore, HER2 positive patients who have received anti-HER2 targeted therapies showed apparent survival benefit compared to those who have not. On the other hand, gene expression analysis revealed overexpression of several gene expression pathways in EMPD tumors when compared with breast cancer tumors, which should be further investigated as potential treatment targets. Regarding immune environment, CD274 (PD-L1) overexpression was observed in EMPD patients, which indicated the potency of therapeutical development using immune check point inhibitors.
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| Free Research Field |
腫瘍診断および治療学関連
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| Academic Significance and Societal Importance of the Research Achievements |
根治切除不能悪性腫瘍は一般的に薬物療法による延命を目的とした治療の対象になるが，希少がんであるEMPDに標準的な治療は存在せず，薬物療法可能な全身状態であっても対症的な支持療法のみ施行されることも多い。今回HER2陽性EMPDでは抗HER2療法を受けた群が支持療法のみ受けた群と比較して明らかな生存期間延長を認めていることが複数例の集積データとして示された。HER2陽性EMPDでは抗HER2療法が有効であることを強く示唆し，新たな標準治療確立につながる重要なデータである。また今回新たに複数の遺伝子経路発現亢進も見つかっており今後新たな治療のターゲットとしてさらなる研究による治療開発が期待される。
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