The incidence of thyroid cancer is rising at the second fastest rate of all malignancies in the United States
and has an increasing tumor-specific mortality annually, making it an important public health problem. The
reasons for this increasing incidence and rising death rate are uncertain. The goal of the P-01 application is
to address the key issues relating to thyroid cancer predisposition, tumorigenesis, and progression in order
to enhance the potential for both early and accurate diagnosis and improve the effectiveness of treatments
for progressive disease. Based on extensive preliminary data from our group, we propose to: (1) examine
and identify predisposing genes for papillary thyroid cancer, (2) determine the critical changes responsible
for the development of follicular thyroid cancer in an inherited form of the disease, Cowden syndrome, using
a novel animal model, and translate this into a scheme to enhance preoperative diagnosis of this form of
thyroid cancer, (3) evaluate and identify the key mechanisms of thyroid cancer induction and
dedifferentiation induced by the RET/PTC 1 oncogene, one of the most common genetic abnormalities in
papillary thyroid cancer, using a second novel animal model system, and (4) determine mechanisms that
regulate tumor invasion and motility for both follicular and papillary thyroid cancers focusing on the models
developed in this P-01, and then test novel agents directed at blocking these pathways. Over the past six
years, the Pis of the individual projects, and the leaders of the cores have created an environment to
successfully perform this integrated P-01 that is unique for thyroid cancer. This includes a substantial
database, integration with pathology, and a record of successful collaborative genetics, laboratory, drug
development, and clinical research as evidenced by approximately thirty co-authored publications. Thus, this
P-01 represents an integrated Bedside-to-Bench-to-Bedside approach targeting the key clinical issues
confronting the diagnosis and management of patients with thyroid cancer. |