Target Therapy in Thyroid Cancer: Current Challenge in Clinical Use of Tyrosine Kinase Inhibitors and Management of Side Effects

Thyroid cancer (TC) is the most common endocrine malignancy. TC is classified as differentiated TC (DTC), which includes papillary and follicular subtypes and Hürthle cell variants, medullary TC (MTC), anaplastic TC (ATC), and poorly differentiated TC (PDTC). The standard of care in DTC consists of surgery together with radioactive iodine ((131)I) therapy and thyroid hormone, but patients with MTC do not benefit from (131)I therapy. Patients with advanced TC resistant to (131)I treatment (RAI-R) have no chance of cure, as well as patients affected by ATC and progressive MTC, in which conventional therapy plays only a palliative role, representing, until a few years ago, an urgent unmet need. In the last decade, a better understanding of molecular pathways involved in the tumorigenesis of specific histopathological subtypes of TC has led to develop tyrosine kinase inhibitors (TKIs). TKIs represent a valid treatment in progressive advanced disease and were tested in all subtypes of TC, highlighting the need to improve progression-free survival. However, treatments using these novel therapeutics are often accompanied by side effects that required optimal management to minimize their toxicities and thereby enable patients who show benefit to continue treatment and obtain maximal clinical efficacy. The goal of this overview is to provide an update on the current use of the main drugs recently studied for advanced TC and the management of the adverse events.