Novel approaches for triple-negative breast cancer using microRNAs that enhance PARP inhibitor sensitivity

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08605
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: Toin University of Yokohama
• Principal Investigator: Okui Michiyo 桐蔭横浜大学, 先端医用工学センター, 講師 (20327654)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: PARP阻害剤 / microRNA

Outline of Final Research Achievements

Poly (ADP-ribose) polymerase inhibitors (PARPi) effectively kill homologous recombination deficient tumor cells through the concept of synthetic lethality. However, PARPi resistance frequently occurs, and therefore additional strategies that synergize with PARPi to enhance anti-tumor activity are necessary. To develop approaches for enhancing the effectiveness of PARPi, we have identified the microRNAs (miR-X, miR-Y and miR-Z) and found that the up-regulation of miR-X, miR-Y and miR-Z suppressed the BRCA1 phosphorylation in human breast cancer cells. These results suggest that miR-X, miR-Y, and miR-Z may improve the chemotherapeutic efficacy of olaparib in BRCA-proficient cancer.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

近年、microRNA（miRNA）が癌抑制因子や癌促進因子として働くことが報告され、そのメカニズムを解明することは新しい治療法を確立する上で欠かすことのできない研究テーマとなっている。olaparib（商品名：Lynparza）はPARP阻害剤の経口薬として期待される一方、耐性獲得などの課題が残されている。申請者は、olaparib感受性を亢進するmiRNA（miR-X、miR-Y、miR-Z）を同定し、これらがヒト乳癌細胞の増殖を抑制することを明らかにした。今後、この細胞増殖抑制メカニズムを解明し、治療の難しいTNBCやHOBCに対して有効なolaparib併用療法の確立に繋げたい。