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

Breast

Sierra Pellizzari¹  Drew Wakeham²  Jennifer Cruickshank³  Kelsey Hodgson⁴  Armen Parsyan⁵  Vasudeva Bhat⁶  David W. Cescon⁶ 

[1] Corresponding author. 268 Grosvenor St, D1-204, London, Ontario, N6A 4V2, Canada.;Department of Anatomy and Cell Biology, London Regional Cancer Program, Western University, London, Ontario, N6A 5C1, 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 Surgery, St Joseph’s Health Care and London Health Sciences Centre, Western University, London, Ontario, N6A 4V2, Canada;Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada;

关键词: Triple-negative breast cancer;    Radiotherapy;    Polo-like kinase 4;    CFI-400945;    Radiosensitization;    Patient-derived organoids;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown