Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy

Oncolytic measles virus (MV) strains have demonstrated broad spectrum preclinical anti-tumor, including breast cancer. Aurora A kinase controls mitotic spindle formation and plays a critical role in malignant transformation. We hypothesized that, by causing mitotic arrest, the Aurora A kinase inhibi...

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Main Authors:	Iankov, Ianko D., Kurokawa, Cheyne B., D’Assoro, Antonio B., Ingle, James N., Domingo-Musibay, Evidio, Allen, Cory, Crosby, Catherine M., Nair, Asha A., Liu, Minetta C., Aderca, Ileana, Federspiel, Mark J., Galanis, Evanthia
Format:	Online
Language:	English
Published:	2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589445/

id	pubmed-4589445
recordtype	oai_dc
spelling	pubmed-45894452016-03-01 Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy Iankov, Ianko D. Kurokawa, Cheyne B. D’Assoro, Antonio B. Ingle, James N. Domingo-Musibay, Evidio Allen, Cory Crosby, Catherine M. Nair, Asha A. Liu, Minetta C. Aderca, Ileana Federspiel, Mark J. Galanis, Evanthia Article Oncolytic measles virus (MV) strains have demonstrated broad spectrum preclinical anti-tumor, including breast cancer. Aurora A kinase controls mitotic spindle formation and plays a critical role in malignant transformation. We hypothesized that, by causing mitotic arrest, the Aurora A kinase inhibitor MLN8237 (alisertib) can increase MV oncolytic effect and efficacy. Alisertib enhanced MV oncolysis in vitro and significantly improved outcome in vivo against breast cancer xenografts. In a disseminated MDA-231-lu-P4 lung metastatic model, the MV/alisertib combination treatment markedly increased median survival to 82.5 days with 20% of the animals being long term survivors vs. 48 days median survival for the control animals. Similarly, in a pleural effusion model of advanced breast cancer, the MV/alisertib combination significantly improved outcome with a 74.5 day median survival versus the single agent groups (57 and 40 days respectively). Increased viral gene expression and IL-24 upregulation were demonstrated, representing possible mechanisms for the observed increase in antitumor effect. Inhibiting Aurora A kinase with alisertib represents a novel approach to enhance measles virus-mediated oncolysis and antitumor effect. Both oncolytic MV strains and alisertib are currently tested in clinical trials, this study therefore provides the basis for translational applications of this combinatorial strategy in the treatment of patients with advanced breast cancer. 2015-08-14 2015-09 /pmc/articles/PMC4589445/ /pubmed/26272026 http://dx.doi.org/10.1038/cgt.2015.36 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Iankov, Ianko D. Kurokawa, Cheyne B. D’Assoro, Antonio B. Ingle, James N. Domingo-Musibay, Evidio Allen, Cory Crosby, Catherine M. Nair, Asha A. Liu, Minetta C. Aderca, Ileana Federspiel, Mark J. Galanis, Evanthia
spellingShingle	Iankov, Ianko D. Kurokawa, Cheyne B. D’Assoro, Antonio B. Ingle, James N. Domingo-Musibay, Evidio Allen, Cory Crosby, Catherine M. Nair, Asha A. Liu, Minetta C. Aderca, Ileana Federspiel, Mark J. Galanis, Evanthia Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
author_facet	Iankov, Ianko D. Kurokawa, Cheyne B. D’Assoro, Antonio B. Ingle, James N. Domingo-Musibay, Evidio Allen, Cory Crosby, Catherine M. Nair, Asha A. Liu, Minetta C. Aderca, Ileana Federspiel, Mark J. Galanis, Evanthia
author_sort	Iankov, Ianko D.
title	Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
title_short	Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
title_full	Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
title_fullStr	Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
title_full_unstemmed	Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
title_sort	inhibition of the aurora a kinase augments the anti-tumor efficacy of oncolytic measles virotherapy
description	Oncolytic measles virus (MV) strains have demonstrated broad spectrum preclinical anti-tumor, including breast cancer. Aurora A kinase controls mitotic spindle formation and plays a critical role in malignant transformation. We hypothesized that, by causing mitotic arrest, the Aurora A kinase inhibitor MLN8237 (alisertib) can increase MV oncolytic effect and efficacy. Alisertib enhanced MV oncolysis in vitro and significantly improved outcome in vivo against breast cancer xenografts. In a disseminated MDA-231-lu-P4 lung metastatic model, the MV/alisertib combination treatment markedly increased median survival to 82.5 days with 20% of the animals being long term survivors vs. 48 days median survival for the control animals. Similarly, in a pleural effusion model of advanced breast cancer, the MV/alisertib combination significantly improved outcome with a 74.5 day median survival versus the single agent groups (57 and 40 days respectively). Increased viral gene expression and IL-24 upregulation were demonstrated, representing possible mechanisms for the observed increase in antitumor effect. Inhibiting Aurora A kinase with alisertib represents a novel approach to enhance measles virus-mediated oncolysis and antitumor effect. Both oncolytic MV strains and alisertib are currently tested in clinical trials, this study therefore provides the basis for translational applications of this combinatorial strategy in the treatment of patients with advanced breast cancer.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589445/
_version_	1613482257300848640

Inhibition of the Aurora A kinase augments the anti-tumor efficacy of oncolytic measles virotherapy

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