Everyone has two copies of the NF 1 gene, which produces a protein called neurofibromin that controls cell division. If both NF 1 genes are defective, not enough neurofibromin is produced, cell division takes off and tumors develop.
"It's like an engine being driven at full speed," said Dr. Clapp.
To encourage development of the blood vessels they need, the tumors emit chemical signals that cause the mast cells to congregate in tissues surrounding the tumors. The mast cells create chemicals called growth factors that enable the creation of blood vessels.
The IU investigators now are identifying drugs that can disrupt the function of mast cells and their proteins in ways that they believe will starve the tumors.
"It's much easier to develop targets against a non-malignant cell than it is the malignant cell itself," said Dr. Clapp. That's because the biological activities of non-malignant cells are stable, while malignant cells are constantly changing due to the genetic instability common to tumors.
By using drugs that target the mast cells' ability to promote blood vessel growth, Clapp and his colleagues hope to prevent tumors from getting larger. Eventually, with continuing treatment, they hope the tumors will shrink or die from lack of blood vessel support.
Neurofibromatosis gets its name from neurofibromas, the disfiguring and often painful tumors that grow along nerve coverings and form on or under the skin. In most patients, the tumors begin to appear in adolescence or adulthood. A patient may develop hundreds of neurofibromas over a lifetime.
Some NF 1 patients also develop numerous light brown (café-au-lait) spots on the skin, enlargement and deformation of bones and curvature of the spine (scoliosis), and in many instances, learning disorders. Occ