放疗联合 Polo 样激酶 4（PLK4）抑制剂 CFI-400945 对三阴性乳腺癌的抗癌作用。

Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer.

机构信息

Department of Surgery, St Joseph's Health Care and London Health Sciences Centre, Western University, London, Ontario, N6A 4V2, Canada; Department of Oncology, Western University, London, Ontario, N6A 5W9, Canada; London Regional Cancer Program, London Health Sciences Centre, Western University, London, Ontario, N6A 5W9, Canada; Department of Anatomy and Cell Biology, London Regional Cancer Program, Western University, London, Ontario, N6A 5C1, Canada.

Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada.

出版信息

Breast. 2021 Aug;58:6-9. doi: 10.1016/j.breast.2021.03.011. Epub 2021 Apr 1.

DOI:10.1016/j.breast.2021.03.011

PMID:33866248

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8079282/

Abstract

Development of novel multimodality radiotherapy treatments in metastatic breast cancer, especially in the most aggressive triple negative (TNBC) subtype, is of significant clinical interest. Here we show that a novel inhibitor of Polo-Like Kinase 4 (PLK4), CFI-400945, in combination with radiation, exhibits a synergistic anti-cancer effect in TNBC cell lines and patient-derived organoids in vitro and leads to a significant increase in survival to tumor endpoint in xenograft models in vivo, compared to control or single-agent treatment. Further preclinical and proof-of-concept clinical studies are warranted to characterize molecular mechanisms of action of this combination and its potential applications in clinical practice.

摘要

开发新型多模态放射治疗转移性乳腺癌，特别是最具侵袭性的三阴性乳腺癌（TNBC）亚型，具有重要的临床意义。在这里，我们表明，一种新型 Polo 样激酶 4（PLK4）抑制剂 CFI-400945 与放射治疗联合使用，在体外 TNBC 细胞系和患者来源的类器官中表现出协同的抗癌作用，并导致在体内异种移植模型中肿瘤终点的生存显著增加，与对照或单药治疗相比。需要进一步进行临床前和概念验证临床研究，以表征这种联合的作用机制及其在临床实践中的潜在应用。