Exploration of Therapeutic Target Pathways Involving DNA Repair Genes in High Grade Serous Ovarian Carcinoma

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K15304
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Asada Kayo 東京大学, 医学部附属病院, 届出研究員 (50805843)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 統合的ゲノム解析 / 卵巣高異型度漿液性癌 / 相同組換修復関連遺伝子変異 / PARP阻害剤

Outline of Final Research Achievements

In this study, we aim to identify mutations and aberrant expression of genes involved in DNA damage repair based on the results of whole exon sequencing, RNA sequencing, and methylation array analysis in 78 cases of high grade serous ovarian carcinoma. The objectives of the research were to identify target factors, and to develop molecularly targeted therapies other than PARP inhibitors that focus on DNA repair mechanisms. As a result, we were able to show that SMYD2 selective inhibitors and immune checkpoint inhibitors may be alternative approaches to ovarian cancer treatment.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

本研究では次世代シーケンサーを用いた解析結果より、卵巣高異型度漿液性癌におけるDNA傷害修復に関わる遺伝子の変異・発現異常を明らかにした。次に、卵巣がん治療に用いられるPARP阻害剤の治療標的として、BRCA1/2以外にヒストンメチルトランスフェラーゼであるSMYD2や、腫瘍免疫に着目した。結果、SMYD2選択的阻害剤や、免疫チェックポイント阻害剤が卵巣がん治療の代替手段となる可能性を示すことが出来た。
加えて、外来子宮鏡の有効性についての検討を進めており、子宮体がんの早期発見にdeep-learningを用いた外来子宮鏡でのAI診断が有用である可能性が示された。