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Endocrine Abstracts (2013) 32 S16.3 | DOI: 10.1530/endoabs.32.S16.3

ECE2013 Symposia Oncogenic signals in thyroid cancer - therapeutic prospects (3 abstracts)

Oncogenic activation in thyroid cancer and response to radioiodine

J Ricarte-Filho


University of Sau Paulo, Sau Paulo, Brazil.


Metastatic thyroid cancer that are radioactive iodine-refractory (RAIR) have a high mortality, particularly if positive on [(18)F]fluorodeoxyglucose (FDG)-positron emission tomography (PET). We now have a better understanding of the genetic alterations implicated in the disease. Several studies along the last years have shown that constitutive activation of the mitogen-activated protein kinase (MAPK), triggered by rearrangements of RET and NTRK1 and activating mutations of RAS and BRAF, has a causal role in these formation of thyroid tumors. We have recently shown that RAIR, FDG-PET-positive metastases are specially enriched for BRAF mutations. Moreover, when BRAF or RAS are mutated in the primary tumor, it is likely that the metastases will harbor the same alteration. Also, we found that metastatic lesions have alterations in genes of the phosphoinositide 3-kinase (PI3K) pathway such as PIK3CA and AKT1, commonly in concomitance with MAPK activation. In contrast to BRAF alterations, PIK3CA/AKT1 mutations status in different specimens from the same patient are frequently divergent because these mutations arise during progression. These findings are important when considering targeted therapies for metastatic tumors. In fact, the use of the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) in patients with metastatic thyroid cancer showed that the drug increases iodine uptake and retention, particularly in RAS-mutant patients. Despite the recent advances and increasing knowledge acquired during the last years, a fraction of these aggressive tumors has no identified driver alterations. The use of the most recent sequencing technologies is helping to uncover the additional genetic changes harbored by these patients.

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