Abstract
Thyroid cancer is the most frequent neoplasm of endocrine system. The major type of thyroid tumor is papillary thyroid carcinoma, in which point mutations in the BRAF and RAS genes and RET/PTC rearrangements are found.
The most frequent molecular genetic changes in follicular thyroid carcinoma are mutations in the RAS genes and PAX8-PPARγ rearrangemets. Point mutations in the RET proto-oncogene are crucial for development of medullary thyroid carcinoma, where germ-line and somatic mutations occur in familial and sporadic form, respectively.
Mutations in the BRAF and RAS genes and moreover mutations in the TP53 and CTNNB1 genes are also detected in the most aggressive anaplastic thyroid carcinoma. Thanks to the finding of genetic causes of thyroid cancer, these genes and their mutations begin to be investigated as promising therapeutic targets.
Many compounds show anti-tumor effect in preclinical studies. The most promising tyrosine kinase inhibitors are Vandetanib, Sunitinib and Sorafenib, which are investigated in thyroid tumor cell-lines, animal models and clinical studies on patients with metastatic stage of thyroid cancer.