Genetic alterations in anaplastic thyroid carcinoma and targeted therapies

Thyroid cancer is the most common type of endocrine malignancy, and its incidence is increasing. Anaplastic thyroid cancer (ATC), referring to undifferentiated subtypes, is considered to be aggressive and associated with poor prognosis. Conventional therapies, including surgery, chemotherapy and radioiodine therapy, have been used for ATC, but these do not provide any significant reduction of the overall mortality rate. The tumorigenesis, development, dedifferentiation and metastasis of ATC are closely associated with the activation of various tyrosine cascades and inactivation of tumor suppressor genes, including B-Raf proto-oncogene, serine/threonine kinase^V600E, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α,tumor protein 53 mutations and telomerase reverse transcriptase mutation. These pathways exert their functions individually or through a complex network. Identification of these mutations may provide a deeper understanding of ATC. A variety of tyrosine kinase inhibitors have been successfully employed for controlling ATC growth in vitro and in xenografts. Certain novel compounds are still in clinical trials. Multi-kinase inhibitors provide a novel approach with great potential. This systematic review determined the prevalence of the major genetic alterations and their inhibitors in ATC.