OncotargetDec 31, 2016

The GSK461364 drug blocking PLK1 shows strong anti-cancer effects in early neuroblastoma tests

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 3, 2026

Abstract

GSK461364 treatment reduced cell viability and proliferation in neuroblastoma models at low doses.

Treatment with GSK461364 caused significant cell cycle arrest and increased apoptosis in neuroblastoma cell lines.
Effects were observed in the low-dose nanomolar range, demonstrating potency independent of MYCN copy number status.
In vivo studies showed that GSK461364 strongly delayed tumor growth in established xenograft models.
The treatment significantly increased survival time in mice receiving GSK461364 compared to control groups.
These findings support the potential of PLK1 inhibitors as a therapeutic option for high-risk neuroblastomas.

Simplified

Polo-like kinase 1 (PLK1) is a serine/threonine kinase that promotes G2/M-phase transition, is expressed in elevated levels in high-risk neuroblastomas and correlates with unfavorable patient outcome. Recently, we and others have presented PLK1 as a potential drug target for neuroblastoma, and reported that the BI2536 PLK1 inhibitor showed antitumoral actvity in preclinical neuroblastoma models. Here we analyzed the effects of GSK461364, a competitive inhibitor for ATP binding to PLK1, on typical tumorigenic properties of preclinical in vitro and in vivo neuroblastoma models. GSK461364 treatment of neuroblastoma cell lines reduced cell viability and proliferative capacity, caused cell cycle arrest and massively induced apoptosis. These phenotypic consequences were induced by treatment in the low-dose nanomolar range, and were independent of MYCN copy number status. GSK461364 treatment strongly delayed established xenograft tumor growth in nude mice, and significantly increased survival time in the treatment group. These preclinical findings indicate PLK1 inhibitors may be effective for patients with high-risk or relapsed neuroblastomas with upregulated PLK1 and might be considered for entry into early phase clinical trials in pediatric patients.

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The GSK461364 drug blocking PLK1 shows strong anti-cancer effects in early neuroblastoma tests

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