CRISPR screens identify novel targets that sensitize prostate cancer cells to ionizing radiation.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K18090
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Osaka University
• Principal Investigator: Hatano Koji 大阪大学, 医学系研究科, 講師 (60762234)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 前立腺癌 / 放射線治療

Outline of Final Research Achievements

Recently, cancer genomics has become important in the selection of treatment for prostate cancer. We performed a comprehensive knockout screen using the CRISPR/cas9 system in prostate cancer cell lines to identify radiosensitizing target genes. We identified top-ranked candidate genes that commonly exhibit radiosensitizing effects in the prostate cancer cell lines (PC3, 22RV1, and LNCaP). By the colony formation assay, the radiosensitization efficacy was confirmed using prostate cancer cells in which radiosensitization target genes are knocked out. The DNA repair after radiation therapy was delayed in the knock-out cells which was confirmed by the γH2AX assay and the Comet assay. Radiosensitivity was restored by knock-in of radiosensitizing target genes into the knock-out cell lines. We are planning additional experiment using mouse model in order to aim for therapeutic application to prostate cancer.

Free Research Field

泌尿器科学

Academic Significance and Societal Importance of the Research Achievements

前立腺癌の治療においてがんゲノムの重要性が高まっている。放射線治療は前立腺癌に対する有効な治療法であり、近年骨転移を来した去勢抵抗性前立腺癌に対するRI内用療法が注目されている。しかし、RI内用療法単独の治療効果は限定的で治療後の再発が問題となる。放射線治療に影響を及ぼすがんゲノムの研究は、治療選択や新たな治療法の確立のためにも意義深い。本研究において、申請者らは放射線治療の感受性に影響を与えるターゲット遺伝子を同定した。この放射線増感ターゲット遺伝子を前立腺癌特異的に抑制することで、正常組織への副作用を軽減しつつ癌への放射線治療効果を高める新規治療法の開発が期待される。