Document Type
Journal Article
Publication Date
11-11-2016
Journal
Scientific Reports
Volume
6
Inclusive Pages
37035
DOI
10.1038/srep37035
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive tumors with low survival rates and the leading cause of death in neurofibromatosis type 1 (NF1) patients under 40 years old. Surgical resection is the standard of care for MPNSTs, but is often incomplete and can generate loss of function, necessitating the development of novel treatment methods for this patient population. Here, we describe a novel combination therapy comprising MEK inhibition and nanoparticle-based photothermal therapy (PTT) for MPNSTs. MEK inhibitors block activity driven by Ras, an oncogene constitutively activated in NF1-associated MPNSTs, while PTT serves as a minimally invasive method to ablate cancer cells. Our rationale for combining these seemingly disparate techniques for MPNSTs is based on several reports demonstrating the efficacy of systemic chemotherapy with local PTT. We combine the MEK inhibitor, PD-0325901 (PD901), with Prussian blue nanoparticles (PBNPs) as PTT agents, to block MEK activity and simultaneously ablate MPNSTs. Our data demonstrate the synergistic effect of combining PD901 with PBNP-based PTT, which converge through the Ras pathway to generate apoptosis, necrosis, and decreased proliferation, thereby mitigating tumor growth and increasing survival of MPNST-bearing animals. Our results suggest the potential of this novel local-systemic combination "nanochemotherapy" for treating patients with MPNSTs.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
APA Citation
Sweeney, E. E., Burga, R. A., Li, C., Zhu, Y., & Fernandes, R. (2016). Photothermal therapy improves the efficacy of a MEK inhibitor in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.. Scientific Reports, 6 (). http://dx.doi.org/10.1038/srep37035
Peer Reviewed
1
Open Access
1
Supplementary Data
Comments
Reproduced with permission of Macmillan Publishers Ltd. Scientific Reports