Circulating Tumor BRAF Mutation and Personalized Thyroid Cancer Treatment

Thyroid cancer is an important malignancy with relatively high incidence among women in middle east (Larijani et al., 2005; Larijani et al., 2004; Mohagheghi et al., 2009) and many part of the world (Salim et al., 2010) like Iran (Sanii et al., 2012; Haghpanah et al., 2006). The incidence has been increasing with rate of up to 3% in countries that reliable cancer registry exits (Morris et al., 2016; Reynolds et al., 2005). In spite of good prognosis of differentiated thyroid carcinoma (DTC), about five to ten percent of patients will develop metastasis and fail to respond to radioactive iodine (RAI), and other traditional therapies (Chen et al., 2009). The lack of effective therapies for DTC, resistant to radioiodine and traditional therapies, is now being overcome by the development of targeted novel compounds (Antonelli, 2014) in the context of personalized treatment. There is strong believe that ctDNA results will be an additional tool while tumor biopsy will remain the gold standard, as it yields important information about tumor type, morphology and origin of tumor, genetic or epigenetic alterations (Saffar et al., 2013; Mohammadi-asl et al., 2011; Sanii et al., 2012). It is still under the debate that circulating tumor markers will take the place of standard tissue biopsy or will support it to guide us to the more effective interventions? BRAFV600E mutation leading to excessive activation of the MAPK pathway accounts for 90% of all cancer-related BRAF mutations and is found in about half of all papillary thyroid cancers (29-69%) and one fourth of anaplastic thyroid cancers (10-35%) (Xing et al., 2013b; Bible and Ryder, 2016). BRAF mutation is completely related to tumors resistance in respond to the first line of treatment which is radioactive iodine (RAI) (Xing et al., 2013a). Vemurafenib is an orally bioavailable, ATP-competitive, small-molecule inhibitor of BRAF kinase with the potential of antineoplastic activity. It selectively binds to the ATP-binding site of BRAF kinase and inhibits its activity, which may result in an inhibition of an over-activated MAPK signaling pathway downstream in BRAFV600Ekinase-expressing tumor cells and a reduction in tumor cell proliferation (Information, (accessed Aug. 20, 2016)). Vemurafenib (Zelboraf; Plexxikon/Roche, with molecular formula:C23H18ClF2N3O3S) joins other multi-targeted kinase inhibitors (MKIs) (Sorafenib, Lenvatinib) and lead to more effective treatment of patients (Brose et al. ; Bollag et al., 2012). LETTER to the EDITOR