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

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

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,...

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Main Authors: Armen Parsyan, Jennifer Cruickshank, Kelsey Hodgson, Drew Wakeham, Sierra Pellizzari, Vasudeva Bhat, David W. Cescon
Format: Article
Language:English
Published: Elsevier 2021-08-01
Series:Breast
Subjects:
Triple-negative breast cancer
Radiotherapy
Polo-like kinase 4
CFI-400945
Radiosensitization
Patient-derived organoids
Online Access:http://www.sciencedirect.com/science/article/pii/S0960977621003507
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spelling doaj-d129a108948546669208676583fd01f12021-06-21T04:23:42ZengElsevierBreast1532-30802021-08-015869Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancerArmen Parsyan0Jennifer Cruickshank1Kelsey Hodgson2Drew Wakeham3Sierra Pellizzari4Vasudeva Bhat5David W. Cescon6Department 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.Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, CanadaPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, CanadaPrincess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, M5G 2C1, CanadaDepartment of Anatomy and Cell Biology, London Regional Cancer Program, Western University, London, Ontario, N6A 5C1, CanadaLondon 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, CanadaPrincess 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, CanadaDevelopment 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.http://www.sciencedirect.com/science/article/pii/S0960977621003507Triple-negative breast cancerRadiotherapyPolo-like kinase 4CFI-400945RadiosensitizationPatient-derived organoids
collection DOAJ
language English
format Article
sources DOAJ
author Armen Parsyan
Jennifer Cruickshank
Kelsey Hodgson
Drew Wakeham
Sierra Pellizzari
Vasudeva Bhat
David W. Cescon
spellingShingle Armen Parsyan
Jennifer Cruickshank
Kelsey Hodgson
Drew Wakeham
Sierra Pellizzari
Vasudeva Bhat
David W. Cescon
Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
Breast
Triple-negative breast cancer
Radiotherapy
Polo-like kinase 4
CFI-400945
Radiosensitization
Patient-derived organoids
author_facet Armen Parsyan
Jennifer Cruickshank
Kelsey Hodgson
Drew Wakeham
Sierra Pellizzari
Vasudeva Bhat
David W. Cescon
author_sort Armen Parsyan
title Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
title_short Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
title_full Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
title_fullStr Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
title_full_unstemmed Anticancer effects of radiation therapy combined with Polo-Like Kinase 4 (PLK4) inhibitor CFI-400945 in triple negative breast cancer
title_sort anticancer effects of radiation therapy combined with polo-like kinase 4 (plk4) inhibitor cfi-400945 in triple negative breast cancer
publisher Elsevier
series Breast
issn 1532-3080
publishDate 2021-08-01
description 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.
topic Triple-negative breast cancer
Radiotherapy
Polo-like kinase 4
CFI-400945
Radiosensitization
Patient-derived organoids
url http://www.sciencedirect.com/science/article/pii/S0960977621003507
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