Abstract
BackgroundErufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Moreover, treatment of nude mice with repeated intraperitoneal or subcutaneous injections of Erufosine is well tolerated and yields drug concentrations in the brain tissue that are higher than the concentrations required for cytotoxic drug effects on glioblastoma cell lines in vitro.MethodsIn the present study we aimed to evaluate the effects of a combined treatment with radiotherapy and Erufosine on growth and local control of T98G subcutaneous glioblastoma xenograft-tumours in NMRI nu/nu mice.ResultsWe show that repeated intraperitoneal injections of Erufosine resulted in a significant drug accumulation in T98G xenograft tumours on NMRI nu/nu mice. Moreover, short-term treatment with 5 intraperitoneal Erufosine injections caused a transient decrease in the growth of T98G tumours without radiotherapy. Furthermore, an increased radiation-induced growth delay of T98G xenograft tumours was observed when fractionated irradiation was combined with short-term Erufosine-treatment. However, no beneficial drug effects on fractionated radiotherapy in terms of local tumour control were observed.ConclusionsWe conclude that short-term treatment with Erufosine is not sufficient to significantly improve local control in combination with radiotherapy in T98G glioblastoma xenograft tumours. Further studies are needed to evaluate efficacy of extended drug treatment schedules.
Highlights
Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro
On the basis of its potent in vitro activity on glioblastoma cell lines alone and in combination with ionizing radiation, and its ability to cross the blood–brain barrier and to accumulate in the brain tissue we aimed to evaluate the effects of a combination of Erufosine and fractionated irradiation on growth and local control of T98G glioblastoma xenograft-tumours in immunodeficient mice
In the present investigation, we show for the first time that short-term treatment with the intravenously applicable Erufosine causes a transient decrease in the growth of the T98G glioblastoma tumours
Summary
Erufosine is a promising anticancer drug that increases the efficacy of radiotherapy in glioblastoma cell lines in vitro. Researchers aim at the Preclinical data suggest alkylphosphocholines (APC) as promising compounds for the treatment of brain tumours, including malignant glioma: Intravenously applicable APCs like Erufosine cross the blood–brain barrier of rats and mice upon repeated parenteral administration of tolerable drug-doses [1,2] and exert potent cytotoxic effects on human glioblastoma cell lines when given alone or in combination with radiotherapy in vitro [3]. Agents of this drug family have a particular mechanism of action: In contrast to DNA-damaging drugs and radiotherapy, they primarily target cellular membranes thereby affecting signal transduction pathways involved in the regulation of proliferation, differentiation and survival of tumour cells [4]. APC induce apoptosis independently of wild type p53 [9,10] suggesting activity in p53-deficient glioblastoma cells
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