Key signaling pathways in papillary thyroid carcinoma

Introduction: Thyroid cancer remains the most common endocrine malignancy worldwide and its incidence and mortality has increased steadily over the last four decades. Improvements in diagnostic techniques that allow a more effective detection of small tumors may account in part for this increase. According to NCCN clinical practiceguidelines in Oncology thyroid carcinoma is categorized into four types: papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC). Description: PTC is the most type of differentiated thyroid carcinoma and accounts for 80–85% of all thyroid carcinomas. PTC can be classified into several variants, among the common of which are the classic variant (CV-PTC), the follicular variant (FV-PTC) and the tall cell variant (TCV-PTC). Genetic alterations in the mitogen-associated protein kinase (MAPK) pathway play an important role in the initiation and progression of PTC, such as , RET/PTC, NTRK (neurotrophic receptor tyrosine kinase) and ALK (anaplastic lymphoma kinase) gene rearrangements or RAS (rat sarcoma) and BRAF (rapidly accelerated fibrosarcoma type-B) activating point mutations, which are almost always found in an exclusive manner, suggesting that oncogenic activation of one member of the pathway is sufficient to drive transformation. Discussion and conclusion: Thyroid carcinogenesis consists of a multiplex process with a large number of molecular alterations among several thyroid neoplasias. The screening for follicular cell-derived specific mutations in association with traditional diagnosis methods has improved the diagnostic accuracy, impacting the prognosis of these tumors. Besides, the advances in the knowledge of the effects of thyroid oncogenes and related mechanisms of action have allowed for the development of multikinase inhibitor targets, promoting new perspectives on therapy to aggressive thyroid tumors.

کلیدواژه ها:

thyroid carcinoma ، PTC ، MAPK pathway ، signaling pathway