Pharmacology and Experimental Therapeutics (Phase I/II):
The goal of the Pharmacology & Experimental Therapeutics (PET) Section is to develop more effective treatments for children and young adults with cancers. Our early clinical trials target children with refractory cancers, for whom no curative treatment exists. Drugs with new and different mechanisms of action are developed in trials called phase I or phase II trials.
Genetic Tumor Predisposition Program: Neurofibromatosis type 1 and medullary thyroid carcinoma:
The PET Section has established a program for neurofibromatosis type 1 (NF1) related tumor and non-tumor manifestations. Neurofibromatosis type 1 is a genetic disorder, which affects 1:3000 individuals. It is characterized by the development of tumors such as neurofibromas, plexiform neurofibromas, optic pathway tumors, juvenile myelomonocytic leukemia (a rare form of leukemia), malignant peripheral nerve sheath tumors (an aggressive type of cancer called a sarcoma), pheochromocytomas (a rare tumor of the adrenal glands, which can cause high blood pressure and flushing). In addition NF1 can manifest in any organ system and can lead to problems such as hypertension (high blood pressure), scoliosis (curvature of the spine), and learning problems.
The PET Section has developed early treatment trials for NF1 related plexiform neurofibromas, which cannot be easily resected, and for patients with a rare type of cancer called malignant peripheral nerve sheath tumors (MPNST). In addition, a natural history trial was developed. This is not a treatment study, and individuals with NF1 are followed regularly for their tumor and non-tumor manifestations. A better understanding of the natural history of NF1-related tumor and other manifestations will be helpful for the development of trial endpoints, the design of treatment studies and the development of effective treatments for NF1.
Multiple endocrine neoplasia (MEN) types 2A and 2B are rare genetic diseases, which lead to the development of medullary thyroid cancer, usually in childhood. Surgery is the only standard treatment. Patients with medullary thyroid cancer can be cured only by thyroidectomy, but only when it is performed at a time when the tumor is confined to the thyroid gland. Traditional chemotherapy is not effective in this cancer. The PET Section has developed a clinical trial with the targeted agent vandetanib for children and young adults with medullary thyroid carcinoma and is currently ongoing.