by Armen Parsyan, Jennifer Cruickshank, Kelsey Hodgson, Drew
Wakeham, Sierra Pellizzari, Vasudeva Bhat, David W. Cescon
The Breast: Published:March
31, 2021
Highlights
The first in class inhibitor of PLK4, CFI-400945, exhibits
synergistic effects with radiation in cell line and patient-derived
organoids in vitro. In MDA-MB-231 xenografts, CFI-400945 sensitizes
to ionizing radiation and significantly improves survival to tumour endpoint
compared to single agent treatments.
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.
