Thyroid cancer

Thyroid cancer (TC) is the most common tumor of the endocrine system. The most frequent type of TC is papillary thyroid cancer (PTC), comprising 90% of all cases. The second most common type is follicular thyroid cancer (FTC) that accounts for 10% of total. PTCs and FTCs both arise from the thyroid follicular cells and are termed differentiated thyroid cancer (DTC). Medullary thyroid cancer (MTC) instead arises from the parafollicular C cells and represents 5% of all TCs. Finally, anaplastic thyroid cancer is one of the most aggressive TCs and can arise from DTCs that dedifferentiate or it can develop de-novo. Ionizing radiation is the only exogenous factor which has been identified as causing TC, mostly the papillary form. PCs frequently have genetic alterations leading to the activation of the MAPK signaling pathway like point mutations of the BRAF and RAS genes and RET/PTC rearrangement. BRAFV600E results in the constitutive activation of this serine/threonine kinase and occurs in approximately 45% of PTCs. Gene translocations resulting in oncogenic rearrangements in PC are best exemplified by more than 10 types of RET–PTC translocations resulting in oncoproteins that activate the MAPK and PI3K–AKT pathways. Most frequent alterations in FC include RAS mutations and PAX8-PARγ rearrangement. Point mutations of RET receptor are crucial for the development of medullary carcinomas. Many of these mutations, particularly those involved in the activation of the MAPK pathway, are being explored as therapeutic targets for thyroid cancer.