Simultaneous PLK1 inhibition improves local tumour control after fractionated irradiation

Autor: Krause, M., Kummer, B., Deparade, A., Eicheler, W., Pfitzmann, D., Yaromina, A., Kunz-Schughart, L. A., Baumann, M.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Radiotherapy and Oncology 108(2013)3, 422-428
Popis: Purpose: Polo-like kinase 1 (PLK1) plays an important role in mitotic progression, is frequently overexpressed and associated with a poor prognosis of cancer patients, thus providing a promising target in anticancer treatment. Aim of the current project was to evaluate the effect of the novel PLK1 inhibitor BI 6727 in combination with irradiation. Material and methods: In vitro proliferation and radiation cell survival assays as well as in vivo local tumour control assays after single treatment and combined radiation and drug application were carried out using the squamous cell carcinoma models A431 and FaDu. In addition, cell cycle phases were monitored in vitro and in vivo. Results: BI 6727 showed a dose-dependent antiproliferative effect and an increase in the mitotic fraction. BI 6727 alone reduced clonogenic cell survival, while radiosensitivity in vitro (SF2) and in vivo (single-dose TCD50 under clamped hypoxia) was not affected. In contrast, local tumour control was significantly improved after application of BI 6727 simultaneously to fractionated irradiation (A431: TCD50 = 60.5 Gy [95% C.I. 57; 63] after IR alone and
Databáze: OpenAIRE