Targeted therapy in metastatic differentiated thyroid Carcinoma (DTC)

Differentiated thyroid carcinoma (DTC), is the most common endocrine malignancy, approximately 3 -- 15% DTC patients have distant metastases at presentation and recurrent disease is diagnosed during the further follow-up in up to 30% of patients, among them distant metastases in 6 -- 23%. Some advanced cases have a poor prognosis, especially cases of radioiodine- refractory or radioiodine-resistant DTC and cases of medullary thyroid cancer (MTC) and anaplastic thyroid cancer (ATC) that are unresectable because they are locally advanced or metastatic, etc., and their prognosis is poor. Preclinical studies have demonstrated that sorafenib inhibits tumor growth in a wide spectrum of human cancers (melanoma, renal, colon, pancreatic, hepatocellular, thyroid, ovarian, and non-small cell lung carcinomas (NSCLCs)) and in some cases induces tumor regression. In 2013, sorafenib was also approved by the FDA to be the first-line treatment option in advanced, radioiodine-refractory differentiated thyroid carcinoma (DTC). Sorafenib inhibits tumor cell proliferation and angiogenesis via targeting numerous serine/threonine and tyrosine kinases (RAF1, BRAF, VEGFR 1, 2, 3, PDGFR, KIT, FLT3, FGFR1, and RET) in multiple oncogenic signaling pathways. Resistance to sorafenib may appear under treatment and may be associated with increased aggressiveness of the neoplasia. In this review, we discuss the clinical pharmacology of sorafenib and highlight genetic variations that may contribute to the diverse pharmacological responses to sorafenib. Better understanding of the factors contributing to the high variability of response to sorafenib should improve the efficacy and safety of the drug, and help select patients who will benefit most from sorafenib therapy.

کلیدواژه ها:

Differentiated thyroid carcinoma ، Sorafenib ، BRAF ، RET ، FGFR1