Molecular and Genetic Markers of Follicular-Cell Thyroid Cancer: Etiology and Diagnostic and Therapeutic Opportunities

Thyroid cancer has an increasing incidence in the US population and worldwide, with 95% of the cancers being of follicular cell origin-papillary, follicular, or anaplastic thyroid carcinomas. Both follicular and papillary thyroid cancers portend good survival rates, with estimated 5-year survival amongst differentiated thyroid cancer approaching 97%. On the other hand, the median survival for a patient with anaplastic thyroid carcinoma is measured in months. Despite the optimistic survival rates for papillary and follicular thyroid carcinoma, a subset of this population demonstrates resistance to radioactive iodine, and a proclivity for more aggressive tumors with higher rates of recurrence and metastasis. As there is an increased understanding of the molecular etiology of thyroid cancer, there is also a new interest in alternative treatment methods for those nonresponsive to typical treatment. Multiple signaling pathways have been identified, including the mitogen activated protein kinase pathway, as crucial to thyroid tumor formation and progression. Additionally, particular oncogenes have been identified as prevalent in anaplastic thyroid carcinoma and thought to be involved in the transformation from differentiated to anaplastic histology. We review the current literature and evidence describing the molecular and genetic etiology of non-medullary ( follicular cell derived) thyroid carcinomas including papillary, follicular, and anaplastic thyroid carcinoma. Additionally, we evaluate the current literature on emerging and established therapies of molecular and genetic targets in these cancers.