Development of synthetic lethal therapy based on gene mutations in renal cancer

Research Project

Project/Area Number	18K07312
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 50020:Tumor diagnostics and therapeutics-related
Research Institution	National Cancer Center Japan
Principal Investigator	Ogiwara Hideaki 国立研究開発法人国立がん研究センター, 研究所, 分野長 (40568953)
Project Period (FY)	2018-04-01 – 2021-03-31
Project Status	Completed (Fiscal Year 2020)
Budget Amount *help	¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000) Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000) Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000) Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords	腎臓がん / PBRM1 / 合成致死性 / 最適化がん治療 / がんゲノム医療 / SETD2 / BAP1 / クロマチンリモデリング / 分子標的治療 / 合成致死 / 個別化治療法
Outline of Final Research Achievements	In this study, we aim to develop the precision medicine for renal clear cell carcinomas by identification of synthetic lethal targets for cancers deficient for chromatin regulator genes PBRM1, SETD2 and BAP1. We identified several synthetic lethal targets for PBRM1-deficient cancers. We would like to elucidate the mechanism of functional relationship between PBRM1 and each of target. And then, we aim for clinical application of synthetic lethal therapy for PBRM1-deficient cancers through the drug and discovery of inhibitors.
Academic Significance and Societal Importance of the Research Achievements	腎臓がんにおける遺伝子異常に基づいた個別化がん治療法は行われていない。PBRM1の遺伝子異常は約40%の腎臓がん患者で見られる。本研究で同定した標的の阻害薬を開発することで、PBRM1遺伝子異常を持つ腎臓がん患者の40％に対する個別化がん治療法の臨床応用が期待できる。さらにPBRM1は腎臓がん以外の胆道がん等の難治性がんでも高頻度異常が認められるため、他のがん種でも個別化治療法の臨床応用が期待できる。