Three-dimensional genomic expression analysis of gynecological multiple cancers and recurrent cancers to reveal oncogenic mechanisms and therapeutic targets

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15576
• 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: Keio University
• Principal Investigator: TAKEDA Takashi 慶應義塾大学, 医学部(信濃町), 特任助教 (60897106)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 重複癌 / Lynch症候群 / 遺伝性乳癌卵巣癌 / 治療抵抗性 / 相同組み換え修復 / オルガノイド

Outline of Final Research Achievements

Synchronous endometrial and ovarian cancer in Lynch syndrome showed that they originated from the respective organs as early cancer, which is contrary to recent reports suggesting that synchronous endometrial and ovarian cancer in the general population is metastatic. Both cancers showed high mutation burden, the characteristic of Lynch syndrome and they would be suitable for immune checkpoint inhibitors. In serous ovarian cancer, common in hereditary breast and ovarian cancer, the homologous recombination repair mechanism that determines the indication for PARP inhibitors can be altered by chemotherapy. This suggests that testing with appropriate specimens is necessary for treatment selection. Currently, we are focusing on developing ovarian tumor initiation organoid models. They can contribute to early diagnosis of ovarian cancer, as well as develop models for other gynecological cancers.

Free Research Field

婦人科癌

Academic Significance and Societal Importance of the Research Achievements

Lynch症候群や遺伝性乳癌卵巣癌など、遺伝的に婦人科癌を発症する疾患では、同時多発的に複数の臓器に癌を生じてくることがあるが、特に子宮内膜、卵巣に同時に癌を生じた場合は、組織型が異なる場合は完全に独立した癌である可能性が高いことが示され、同時に各癌の治療を行うことの重要性と特に明細胞癌における免疫チェックポイント阻害薬の有用性が示唆された。また漿液性卵巣癌においては、PARP阻害剤の適応判断となるHRDステータスが、化学療法によって変動する可能性も示唆され、適切な検体を用いた検査施行が、治療選択に重要であると考えられ、今後の卵巣癌の治療戦略構築に影響するものと考えられた。