Neurofibromatosis type 1 (NF1) is one of the most common inherited disorders throughout the world and is estimated to affect about 100,000 people in the United States alone. It is genetic and is passed down from generation to generation. Individuals with NF1 have a defect or mutation in an important gene known as the NF1 tumor suppressor gene. This gene is important because it makes a protein, called neurofibromin, which functions to prevent cancer. People with NF1 cannot make enough neurofibromin or make an altered form of neurofibromin that does not work properly. Because of this people with NF1 can develop tumors or cancers that can be benign (nonaggressive) or malignant (aggressive). Benign tumors, called neurofibromas, are the most common and can be located in a variety of places. Cutaneous neurofibromas reside under the skin. Plexiform neurofibromas lie deep within the soft tissues or organs and are usually near nerves. Optic gliomas occur near nerves near the eyes. These tumors are very difficult to treat and do not respond well to chemotherapy. Physicians try to avoid using radiation therapy because people with NF1 who receive radiation therapy have a much higher risk of developing secondary cancers following radiation treatments compared to people without NF1. Because neurofibromas tend to have a large blood supply, these tumors are difficult for surgeons to remove and have a high risk for bleeding during the operation. Because of these issues, a new kind of treatment is necessary to treat the tumors that people with NF1 develop.
Years ago, it was noticed that the tumors in people with NF1 have a lot of a specific kind of immune cell called mast cells. These mast cells are known to be important in diseases such as allergic reactions. Scientists thought that these mast cells have an immunological role in helping or allowing these particular tumors to grow. Therefore, scientists thought that they might be able to treat these tumors by controlling the mast cells, which seem to be very common in these tumors. They did this by using drugs called c-Kit inhibitors. These drugs prevent a specific enzyme called c-Kit from working in the bone marrow and preventing mast cells from being activated. There are several drugs that do this, and these drugs were tested on animals that were genetically designed to make the same NF1 tumors that people with NF1 have. Many of the drugs that work on the enzyme c-Kit were tested and we think that a particular one called Sutent, also known as Sunitinib, is the best to test in people. It is already being used in people to treat a few different types of cancers and we know what the side effects are, the safe dose to give, and how often to give it so that it is safe. Using genetically defective mouse models with NF1 who make tumors similar to the tumors formed in humans with NF1, we have shown that Sutent decreases the number of tumors formed as well as the size of these tumors. We want to try this drug on people with NF1 and deep neurofibromas (called plexiform neurofibromas) who are having problems because of their tumors. We hope that if this drug works we will be able to help the thousands of people with NF1 and to treat their tumors effectively.