Treatment of NF1-Driven Neurofibromas Through VDR-Mediated Stromal Reprograming
Abstract
Virtually every patient diagnosed with neurofibromatosis is faced with the challenge of managing neurofibroma tumor growth. This can range from the emotional difficulties of cosmetically disfiguring dermal neurofibromas to the more painful growth of deep-tissue plexiform neurofibromas. In addition, a subset of these neurofibromas can undergo “malignant conversion” and transform into a rapidly growing and potentially lethal tumor type known as malignant peripheral nerve sheath tumors. Importantly, while decades of research have focused largely on identifying and targeting the tumor cells that define this disease, tumor masses are not just simply made up of tumor cells, but are also comprised of a recruited network of support cells known as stroma. Nevertheless, very little is known about how stromal cells function to assist the growth of neurofibromas and their malignant conversion. Here we propose to take a radically new approach to target to neurofibromatosis-associated tumors by breaking down their stromal support network with a clinically approved class of drugs that targets the vitamin D receptor (VDR). We will test whether this VDR stromal remodeling therapy is sufficient to impact tumor growth on its own and explore its potential to work in combination with clinically approved MEK inhibitors. Of particular relevance for patients, VDR therapies are relatively safe for long-term treatment and are already available in the clinic, allowing this work to immediately translate into clinical trials.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910552
Entities
People
- Ronald Evans
Organizations
- Salk Institute for Biological Studies
- United States Army