Cabazitaxel operates anti-metastatic and cytotoxic via apoptosis induction and stalls brain tumor angiogenesis.

Taxanes target microtubules and are clinically established chemotherapeutic agents with proven efficacy in human cancers. Cabazitaxel (XRP-6258, Jevtana®) is a second generation semisynthetic taxane with high chemotherapeutic potential in prostate cancer. There, cabazitaxel can overcome docetaxel-resistant prostate cancer. Here, we tested the effects of cabazitaxel on glioma cells, and non-transformed cells such as neurons and astrocytes. Cabazitaxel operates highly toxic in various human glioma cells at nanomolar concentrations. In contrast, primary astrocytes and neurons are not affected by this agent. Cabazitaxel disrupts cytoskeletal F-actin fibers and induces apoptotic cell death in gliomas. Moreover, cabazitaxel displayed highest efficacy in inhibiting glioma cell migration and invasion. Here we demonstrate that cabazitaxel inhibited tumor migration already at 1 nM. We also tested cabazitaxel in the ex vivo VOGiM assay. Cabazitaxel stalled glioma growth and at the same time inhibited tumor-induced angiogenesis. In summary, we found that cabazitaxel operates as an apoptosis-inducing gliomatoxic agent with strongest effects on migration and invasive growth. Thus, our report uncovered cabazitaxel actions on gliomas and on the brain tumor microenvironment. These data reveal novel aspects for adjuvant approaches when applied to brain tumor patients.

Oncotarget. 2016 May 18 [Epub ahead of print]

Ali Ghoochani, Gökce Hatipoglu-Majernik, Tina Sehm, Sven Wach, Michael Buchfelder, Helge Taubert, Ilker Y Eyupoglu, Nicolai Savaskan

Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany., Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany., Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany., Department of Urology, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg Erlangen, Germany., Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany., Department of Urology, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg Erlangen, Germany., Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany., Translational Cell Biology & Neurooncology Lab, Department of Neurosurgery, Universitätsklinikum Erlangen, Medical School of the Friedrich-Alexander University (FAU) of Erlangen - Nürnberg, D-91054 Erlangen, Germany.