Targeting PIM Kinase As a Therapeutic Strategy in Human Hepatoblastoma

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jun 2

PMID 29854306

Citations 20

Authors

Laura L Stafman

Smitha Mruthyunjayappa

Alicia M Waters

Evan F Garner

Jamie M Aye

Jerry E Stewart

Karina J Yoon

Kimberly Whelan

Elizabeth Mroczek-Musulman

Elizabeth A Beierle

Affiliations

Soon will be listed here.

Abstract

Increasing incidence coupled with poor prognosis and treatments that are virtually unchanged over the past 20 years have made the need for the development of novel therapeutics for hepatoblastoma imperative. PIM kinases have been implicated as drivers of tumorigenesis in multiple cancers, including hepatocellular carcinoma. We hypothesized that PIM kinases, specifically PIM3, would play a role in hepatoblastoma tumorigenesis and that PIM kinase inhibition would affect hepatoblastoma and . Parameters including cell survival, proliferation, motility, and apoptosis were assessed in human hepatoblastoma cells following PIM3 knockdown with siRNA or treatment with the PIM inhibitor AZD1208. An model of human hepatoblastoma was utilized to study the effects of PIM inhibition alone and in combination with cisplatin. PIM kinases were found to be present in the human hepatoblastoma cell line, HuH6, and in a human hepatoblastoma patient-derived xenograft, COA67. PIM3 knockdown or inhibition with AZD1208 decreased cell survival, attachment independent growth, and motility. Additionally, inhibition of tumor growth was observed in a hepatoblastoma xenograft model in mice treated with AZD1208. Combination therapy with AZD1208 and cisplatin resulted in a significant increase in animal survival when compared to either treatment alone. The current studies showed that PIM kinase inhibition decreased human hepatoblastoma tumorigenicity both and , implying that PIM inhibitors may be useful as a novel therapeutic for children with hepatoblastoma.

Citing Articles

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PIM Kinase Inhibition Attenuates the Malignant Progression of Metastatic Hepatoblastoma.

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