Epithelial thyroid carcinomas (TC) account for more than 90% of all endocrine malignancies and represent one of the most frequent cancers in women. They include the well-differentiated TC (DTC), comprising the papillary (PTC) and follicular (FTC) histotypes, the poorly differentiated (PDTC), and the undifferentiated or anaplastic TC (ATC). Both PDTC and ATC are aggressive human neoplasms with a dire prognosis due to the absence of effective therapies, which makes mandatory the identification of novel therapeutic strategies. Intrinsic chromosomal instability (CIN, an increased rate of gain or losses of chromosomes during cell division) is a common feature of solid tumors and represents a major driving force in thyroid cancer progression, thought to be responsible for the acquisition by malignant cells of novel functional capabilities. Different mitotic kinases, whose expression or function has been found altered in human cancer tissues, are major drivers of thyroid tumor aneuploidy. Among these are the three members of the Aurora family (Aurora-A, Aurora-B and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed with promising antitumor effects in preclinical and clinical studies against different human cancers, including TC. Here, we will focus on the Aurora mitotic functions in normal cells; we shall then describe the main implications of their overexpression in the onset of genetic instability and aneuploidy. We will finally describe the consequences of Aurora kinase inhibition on TC cell growth and tumorigenicity.
Part of the book: Anti-cancer Drugs