Establishment of organoid culture and development of treatment strategies in gastric-type adenocarcinoma of the cervix

2022 Fiscal Year Final Research Report

• 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
• Keywords: HPV / 子宮頸癌 / オルガノイド培養

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.

Free Research Field

婦人科腫瘍

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。