Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283

William Petersen; Jingbo Liu; Liangping Yuan; Hongying Zhang; Matthew Schneiderjan; Yoon Jae Cho; Tobey J. MacDonald

doi:10.1016/j.canlet.2014.07.038

Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283

William Petersen, Jingbo Liu, Liangping Yuan, Hongying Zhang, Matthew Schneiderjan, Yoon Jae Cho, Tobey J. MacDonald

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

Abstract

Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.

Original language	English (US)
Pages (from-to)	68-76
Number of pages	9
Journal	Cancer Letters
Volume	354
Issue number	1
DOIs	https://doi.org/10.1016/j.canlet.2014.07.038
State	Published - Nov 1 2014
Externally published	Yes

Keywords

Aurora kinase
Dasatinib
Medulloblastoma
Survival

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1016/j.canlet.2014.07.038

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title = "Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283",

abstract = "Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.",

keywords = "Aurora kinase, Dasatinib, Medulloblastoma, Survival",

author = "William Petersen and Jingbo Liu and Liangping Yuan and Hongying Zhang and Matthew Schneiderjan and Cho, {Yoon Jae} and MacDonald, {Tobey J.}",

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T1 - Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283

AU - Petersen, William

AU - Liu, Jingbo

AU - Yuan, Liangping

AU - Zhang, Hongying

AU - Schneiderjan, Matthew

AU - Cho, Yoon Jae

AU - MacDonald, Tobey J.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.

AB - Medulloblastoma (MB) expresses Src kinase, while aurora kinase A overexpression correlates with poor survival. We thus investigated novel combination treatment with dasatinib and AT9283, inhibitors of Src and aurora kinase, respectively, on MB growth in vitro and in vivo. Treatment with each drug significantly reduced cell viability and combined treatment markedly potentiated this response. AT9283 induced p53 expression, autophagy, and G2/M cell-cycle arrest, while combined treatment induced S phase arrest. Dasatinib treatment caused tumor regression in vivo. Activated Src was detected in 44% MB analyzed. We conclude that further evaluation of this combination therapy for MB is highly warranted.

KW - Aurora kinase

KW - Dasatinib

KW - Medulloblastoma

KW - Survival

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Dasatinib suppression of medulloblastoma survival and migration is markedly enhanced by combining treatment with the aurora kinase inhibitor AT9283

Abstract

Keywords

ASJC Scopus subject areas

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