| 研究課題/領域番号 |
21K15498
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分50010:腫瘍生物学関連
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| 研究機関 | 国立研究開発法人国立がん研究センター |
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研究代表者 |
カポダッノ イレニア 国立研究開発法人国立がん研究センター, 研究所, 特任研究員 (60889187)
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| 研究期間 (年度) |
2021-04-01 – 2022-03-31
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| 研究課題ステータス |
中途終了 (2021年度)
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| 配分額 *注記 |
3,250千円 (直接経費: 2,500千円、間接経費: 750千円)
2022年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
2021年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
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| キーワード | notch pathway / p53 / diagnostic marker / MEN1 / cancer stem cells / PNETs / diagnostic markers / metastases |
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| 研究開始時の研究の概要 |
Pancreatic neuroendocrine tumors are rare tumors that arise from hormone-producing cells in the pancreas. For these tumors, no curative treatment is currently available. The aim of this study is to identify novel drug targets for improving the outcome of patients diagnosed with this rare disease.
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| 研究実績の概要 |
Pancreatic neuroendocrine tumors (PanNETs) are highly heterogeneous tumors and for this reason developing a curative treatment has been proven challenging. Genomic analysis revealed that these tumors often do not harbor mutations in typical cancer-related genes such as p53. Although they harbor mutation in unique PanNET-related genes such as MEN-1. Still, much knowledge is missing on the mechanisms of tumorigenesis and specifically on the heterogeneity of these tumors. Using a multimodal approach in this project I have analysed both the inter- and intra- tumor heterogeneity and I have identified some of the crucial nodes of PanNET tumorogenesis. Specifically, I have demonstrated that the Notch pathway and p53 intertwine in PanNET to promote tumorigenesis when MEN-1 mutations occur. Most interestingly, I have identified insulinoma associated-1 (INSM1) as a key marker of proliferation in PanNET early onset when MEN1 is lost and p53 is wildtype.
These data suggest that specific genomic alterations in PanNETs influence their tumorigenesis. Considering the current lack of a system to stratify all PanNET patients based on their genomic abnormalities, these findings may thereby provide an opportunity to improve future clinical decisions and improve the prognosis of PanNET patients.
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