**Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers**

Enke Baldini, Chiara Tuccilli, Salvatore Sorrenti, Domenico Mascagni, Stefano Arcieri, Angelo Filippini and Salvatore Ulisse Enke Baldini, Chiara Tuccilli, Salvatore Sorrenti, Domenico Mascagni, Stefano Arcieri, Angelo Filippini and Salvatore Ulisse

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64597

#### **Abstract**

[64] Howard EW, Camm KD, Wong YC, Wang XH: E-cadherin upregulation as a therapeutic

[65] Margosio B, Rusnati M, Bonezzi K, Cordes BL, Annis DS, Urbinati C, Giavazzi R, Presta M, Ribatti D, Mosher DF, et al.: Fibroblast growth factor-2 binding to the thrombospondin-1 type III repeats, a novel antiangiogenic domain. Int J Biochem Cell Biol. 2008;

[66] Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for

[67] Albert DH, Tapang P, Magoc TJ, Pease LJ, Reuter DR, Wei RQ, Li J, Guo J, Bousquet PF, Ghoreishi-Haack NS, et al.: Preclinical activity of ABT-869, a multitargeted receptor

goal in cancer treatment. Mini Rev Med Chem. 2008; 8:496–518.

treating cancer. Nat Rev Drug Discov. 2006; 5:835–844.

tyrosine kinase inhibitor. Mol Cancer Ther. 2006; 5:995–1006.

40:700–709.

94 Anti-cancer Drugs - Nature, Synthesis and Cell

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.

**Keywords:** thyroid cancers, Aurora kinases, mitosis, therapy, Aurora kinase inhibitors

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
