Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer. (August 2021)

• Record Type: Journal Article
• Authors: Parsyan, Armen; Cruickshank, Jennifer; Hodgson, Kelsey; Wakeham, Drew; Pellizzari, Sierra; Bhat, Vasudeva; Cescon, David W.
• Is Part Of: Breast. Volume 58(2021)
• Page Start: 6
• Page End: 9
• Publication Date: 2021-08
• Subjects: Triple-negative breast cancer -- Radiotherapy -- Polo-like kinase 4 -- CFI-400945 -- Radiosensitization -- Patient-derived organoids; Breast -- Diseases -- Periodicals; Breast -- Tumors -- Periodicals; Breast -- Periodicals; Electronic journals; Periodicals; 616
• DOI: 10.1016/j.breast.2021.03.011
• Languages: English
• ISSNs: 0960-9776

Abstract

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. Highlights: PLK4 inhibitor CFI-400945, combined with radiation, shows synergistic antiproliferative activity in immortalized breast cancer cell lines. CFI-400945 in combination with radiation shows synergistic antiproliferative activity in breast cancer patient-derived organoids. In MDA-MB-231 xenograft mice, CFI-400945 sensitizes to radiation and significantly improves survival to the tumour endpoint.