Development of therapeutics targeting DNA damage repair pathway in uterine neoplasms

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K21330
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology; Tumor therapeutics
• Research Institution: The University of Tokyo
• Principal Investigator: Miyasaka Aki 東京大学, 医学部附属病院, 登録研究員 (10754997)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 子宮腫瘍 / クリニカルシークエンス / 相同組換修復 / PARP阻害薬

Outline of Final Research Achievements

Uterine sarcomas are rare malignant uterine neoplasms. Their rarity and histopathological diversity have contributed to the lack of consensus on risk factors for poor outcome and optimal treatment. Genome sequencing is a comprehensive method for analyzing entire genomes, which is a powerful tool for elucidating pathological conditions and developing treatments. “Onco-panel for gene profiling” is a sequencing that can comprehensively analyze about mutations of five hundred at a time using a next-generation sequencing. Whether the found mutations were clinically significant was judged from the gene database. It has been suggested that treatment targeting the DNA damage repair pathway such as PARP inhibitor may be effective for uterine sarcoma.

Free Research Field

婦人科腫瘍

Academic Significance and Societal Importance of the Research Achievements

子宮肉腫は稀少であり、その病理病態が未解明な腫瘍である。治療法は確立されておらず、予後も不良である。肉腫の診断及び新規治療の開発に関して、治療法の開発は急務である。全エクソンシークエンス・全ゲノムシークエンス・RNA-Seq等を個別の症例において適宜行うことにより、ドライバー変異や治療標的になりうる体細胞変異の検索を行うことが可能である。個々の症例の蓄積が、稀少疾患に最適なクリニカルシークエンス検査の構築や新規治療の開発につながる。その導入としての今回の研究は学術的、および社会的にも有意義であると考えられる。