NeOnc Technologies Holdings conducted a study to examine the effects of its NEO212 formulation in helping to block one of the key processes in cancer tumor growth. In tumor cells, the endothelial-to-mesenchymal transition (EndMT) supports the pro-angiogenic and invasive characteristics of glioblastoma multiforme (GBM). Blocking this process would be a promising approach to inhibit tumor progression and recurrence. In the study, NeOnc was able to demonstrate that glioma stem cells (GSC) induce EndMT in brain endothelial cells (BEC). TGF-β signaling is necessary, but not sufficient to induce this EndMT process. Cell-to-cell contact and the contribution of Notch signaling are also required. NEO212, a conjugate of temozolomide and perillyl alcohol, blocks EndMT induction and reverts the mesenchymal phenotype of tumor-associated BEC (TuBEC) by blocking TGF-β and Notch pathways. Consequently, NEO212 reduces the invasiveness and proangiogenic properties associated with TuBEC, without affecting control BEC. Intracranial co-implantation of BEC and GSC in athymic mice showed that EndMT occurs in vivo, and can be blocked by NEO212, supporting the potential clinical value of NEO212 for the treatment of GBM.

The study confirms that lower concentrations of NEO212 have effects independent of the cytotoxicity caused by higher doses [10]. This is very unusual in chemotherapy and suggests that lower concentrations of NEO212 may be used for treating other manifestations of GBM, including invasion and EndMT.

Read The Paper

NEO212, a conjugate of temozolomide and perillyl alcohol, blocks the endothelial-to-mesenchymal transition in tumor-associated brain endothelial cells in glioblastoma.

Authors: Nagore ^I. Marín-Ramos¹, Niyati Jhaveri¹, Thu Zan Thein¹, Rochelle A. Fayngor¹, Thomas C. Che^1,2, Florence M. Hofman^1,2,∗

¹ Department of Neurosurgery, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
² Department of Pathology, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA
^* Corresponding author. Departments of Pathology and Neurosurgery, Keck School of Medicine, University of Southern California, 2011 Zonal Avenue, Los Angeles, CA 90033, USA