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Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.


Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)

 I love this type of research.  Invadopoia are small projections from the edges of tumnor cells that help allow them to move.  Without the ability to move, the tumor is much less dangerous and more sensitive to normal treatments. This is a highly underappreciated target and they found 2 existing drugs which may target this.  Of course, it is just theory now and needs to be tested but it is a promising approach!


Posted on: 09/17/2018

Transl Oncol. 2018 Sep 13;11(6):1406-1418. doi: 10.1016/j.tranon.2018.08.012. [Epub ahead of print]
Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.
Whitehead CA1, Nguyen HPT1, Morokoff AP2, Luwor RB 1, Paradiso L1, Kaye AH2, Mantamadiotis T3, Stylli SS4.
 
Author information:
1. Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
2. Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia.
3. Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Department of Microbiology & Immunology, School of Biomedical Sciences, The University of Melbourne, Parkville VIC 3010, Victoria, Australia.
4. Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Electronic address: stanley.stylli@mh.org.au.
Abstract
 
The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopodia" and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome.

 




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