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Understanding the Mechanism of Late Sorafenib Failure in Metastatic Thyroid Cancer

Results – pAkt Conclusions Thyroid cancer: Thyroid cancer is the most common endocrine neoplasm, accounting for approximately 2.5% of all new noncutaneous malignancies. Approximately 90% of thyroid cancers are well differentiated, with most of these having favorable prognosis. A subset of patients have aggressive malignancies refractory to surgical and iodine therapy; in these patients clinical trials are underway evaluating targeted molecular therapy. Sorafenib: Sorafenib specifically inhibits the serine/threonine kinases RAF-1 and BRAF, the tyrosine kinase receptors VEGFR-2, VEGFR-3, PDGFRβ, Flt-3, KIT, in addition to RET kinase activity. Sorafenib has been shown to abrogate tumor progression in renal cell carcinoma and hepatocellular carcinoma. Our group has previously shown clinical response with sorafenib in unresectable thyroid cancer, although there were no patients with complete oncologic response. As part of an ongoing study, we used immunohistochemistry to investigate the mechanisms of sorafenib resistance in a patient with unresectable, tall cell variant of papillary thyroid cancer.