Chapters authored
Emerging Therapeutic Approaches for the Most Aggressive Epithelial Thyroid Cancers
The majority of epithelial thyroid carcinomas (TC) have a differentiated (DTC) histotype and include the papillary (PTC) and the follicular (FTC) TC which, ensuing dedifferentiation, generate the aggressive poorly differentiated (PDTC) and anaplastic (ATC) TC. Although derived from the same cell type, each TC shows specific histological features, biological behavior, and degree of differentiation because of different genetic alterations. Total thyroidectomy, followed by adjuvant therapy with 131I, is the treatment of choice for most patients affected by DTC. The prognosis of DTC patients is favorable, with 10‐year survival rate of nearly 90%. However, one third of them face the morbidity of disease recurrence and TC‐related deaths. The worst outcomes are encountered in patients with PDTC and ATC. The latter, in particular, has a mean survival time of few months from the diagnosis, which is not influenced by current anticancer treatments. Following the progress made in the comprehension of the underlying molecular mechanisms deregulated in TC progression, novel therapeutic approaches have come to light. Here, we will attempt to review new targeted therapies, which are currently being exploited in preclinical and clinical studies, with tyrosine kinase inhibitors as well as with emerging inhibitors of mitotic kinases, in PDTC and ATC.
Part of the book: Thyroid Cancer
Aurora Kinases: New Molecular Targets for the Therapy of Aggressive Thyroid Cancers
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