| Project/Area Number |
20K18157
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Taguchi Ayumi 東京大学, 医学部附属病院, 届出研究員 (60756782)
|
|---|
| Project Period (FY) |
2020-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | HPV / 子宮頸癌 / オルガノイド培養 / 子宮頸がん / プレシジョンメディシン / オルガノイド |
|---|
| Outline of Research at the Start |
子宮頸部胃型腺癌の手術検体をマトリゲル培養することでオルガノイドを作製し、組織免疫染色と網羅的発現解析やゲノム解析によってprofilingする。さらに、新規治療薬の探索として、PARP阻害剤であるniraparibとolaparibのオルガノイドに対する効果を検討する。
|
| Outline of Final Research Achievements |
We have established organoid cultures in one case of squamous cell carcinoma of the cervix, three cases of adenosquamous carcinoma, and one case of small cell carcinoma. We performed whole exome sequencing (WES) and RNA-sequencing analysis of HPV18-positive small cell carcinoma, a rare and refractory cancer, to search for potential therapeutic targets. WES analysis identified a pathogenic variant in KRAS p.G12D. RNA-seq analysis also confirmed that the HPV18 genome was integrated into chromosome 8 (8q24.21), accompanied by high expression of the downstream MYC gene. Drug sensitivity testing using organoid cultures with the KRAS mutation and high MYC expression as therapeutic targets showed high antitumor efficacy with trametinib, a KRAS pathway inhibitor.
|
| Academic Significance and Societal Importance of the Research Achievements |
子宮頸癌の中で胃型腺癌や小細胞癌は希少癌でかつ難治性癌であり、その治療法の確立は喫緊の課題であった。本研究では、子宮頸部小細胞癌のゲノム解析、トランスクリプトーム解析から治療標的の絞り込みを行い、さらにオルガノイド培養を用いることで薬剤感受性試験を行うことができた。治療標的の同定と患者由来モデルを用いた薬剤感受性試験の一連の流れの確立は今後のがん医療における個別化療法の基盤となっていくことが期待される。
|
