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In vitro and in vivo Investigations of New Anticancer Agents
- PDGF receptor antagonists
Glioblastoma are known to exhibit numerous genetic and
physiological peculiarities such as the coexpression of
platelet-derived growth factors (PDGF) and their receptors (PDGFR). The
inhibition of the growth of human glioblastoma cells by disruption of
the PDGF/PDGFR autocrine loops was reported as well as the inhibition
of subcutaneous and intracranial tumours in nude mice, suggesting that
PDGF receptors might be a therapeutic target for glioblastoma.
We studied the effect of imatinib, leflunomide and AG-1296 on different
malignant human brain tumours in vitro at therapeutically relevant
concentrations. Our results suggest that clinical antitumor effects of
imatinib on glioblastoma, if any, are not mediated by the PDGFR.
- Kinesin inhibitors
The inhibition of kinesin Eg5 by small molecules such
as monastrol is currently evaluated as an approach to develop a new
class of antiproliferative drugs for the treatment of malignant
tumours. In this project we investigated the effect of new monastrol
analogs on human glioblastoma cells. These compounds induced mitotic
arrest in glioblastoma cells but had no effect on the cyto-skeleton of
quiescent cells. Thus, compared to classical tubulin inhibitors, the
new kinesin inhibitors may exhibit less neurotoxic clinical effects.
Collaboration with Prof. A. Giannis (Organic Chemistry, University of Leipzig)
Recent publications:
- C. Müller, D. Gross, V. Sarli, M. Gartner, A. Giannis, G.
Bernhardt, A. Buschauer, Inhibitors of kinesin Eg5: antiproliferative
activity of monastrol analogues against human glioblastoma cells. Cancer Chemother. Pharmacol. 59 (2), 157-164 (2007).
- D. Gross, G. Bernhardt, A. Buschauer, Platelet-derived growth
factor receptor independent proliferation of human glioblastoma cells:
selective tyrosine kinase inhibitors lack antiproliferative activity. J. Cancer Res. Clin. Oncol. 132 (9), 589-599 (2006).
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