CRISPR screen reveals novel target genes in prostate cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20806
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: Osaka Medical and Pharmaceutical University
• Principal Investigator: Tsujino Takuya 大阪医科薬科大学, 医学部, 助教 (60937407)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 前立腺がん / PARP阻害 / CRISPRスクリーニング

Outline of Final Research Achievements

In our CRISPR screening analysis combined with PARP inhibitor therapy in prostate cancer cell lines, we identified 67 sensitivity-related genes and 103 resistance-related genes. The identified sensitivity-related genes are mainly associated with DNA repair pathways, and more than 10 genes, including the MMS22L gene, have been elucidated as genetic biomarkers that confer high sensitivity to PARP inhibitors. Additionally, as resistance genes, 7 genes including the RB1 gene and CHEK2 gene have been elucidated as genetic biomarkers associated with PARP inhibitor resistance. These results represent the first comprehensive report on genetic biomarkers for PARP inhibitors in prostate cancer.

Free Research Field

腫瘍

Academic Significance and Societal Importance of the Research Achievements

これまでPARP阻害剤の有効性はBRCA1/2遺伝子変異のみに限定されており、現在その拡充、および耐性克服が課題となっている。本研究における成果により、PARP阻害剤の有用性拡大の可能性が示されたと同時に、耐性克服を可能とする新規治療法開発に繋がると考えられる。本成果は、前立腺がんPARP阻害剤治療包括的遺伝子バイオマーカーを同定した初報告であり、その研究発展性は非常に高く、転移性去勢抵抗性前立腺がんの予後改善に繋がる成果であると考えられる。