Abstract
Background: Thyroid cancer is a common malignancy whose detection has increased significantly in past decades. Most of the increased incidence is due to detection of early well-differentiated thyroid cancer, but the incidence of more advanced thyroid cancers has increased as well. Recent methodological advancements have allowed for a deep understanding of the molecular underpinnings of the various types of thyroid cancer. Summary: Thyroid cancers harbor a high frequency of potential druggable molecular alterations, including the highest frequency of oncogenic driver kinase fusions seen across all solid tumors. Analyses of poorly differentiated and anaplastic thyroid carcinoma confirmed that these tumors develop from more well-differentiated follicular-derived thyroid cancers through acquired additional mutations. The recognition of driver genomic alterations in thyroid cancers not only predicts tumor phenotype but also now can inform treatment approaches. Conclusions: Major progress in understanding the oncogenic molecular underpinnings across the array of thyroid cancers has led to considerable gains in gene-specific systemic therapies for many cancers. This article focuses on the molecular characteristics of aggressive follicular-derived thyroid cancers and medullary thyroid cancer and highlights advancements in treating thyroid cancer in the era of targeted therapy.