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

Armen Parsyan; Jennifer Cruickshank; Kelsey Hodgson; Drew Wakeham; Sierra Pellizzari; Vasudeva Bhat; David W. Cescon

Breast (Aug 2021)

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

Armen Parsyan,
Jennifer Cruickshank,
Kelsey Hodgson,
Drew Wakeham,
Sierra Pellizzari,
Vasudeva Bhat,
David W. Cescon

Affiliations

Armen Parsyan: 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; Corresponding author. 268 Grosvenor St, D1-204, London, Ontario, N6A 4V2, Canada.
Jennifer Cruickshank: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada
Kelsey Hodgson: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada
Drew Wakeham: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada
Sierra Pellizzari: Department of Anatomy and Cell Biology, London Regional Cancer Program, Western University, London, Ontario, N6A 5C1, Canada
Vasudeva Bhat: 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
David W. Cescon: Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada; Department of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, Canada

Journal volume & issue: Vol. 58
pp. 6 – 9

Abstract

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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.

Published in Breast

ISSN: 1532-3080 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/the-breast

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