A New Aurora in Anaplastic Thyroid Cancer Therapy

Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include 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, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation

Prevalence of Extra-Thyroidal Malignancies in Patients Positive (n = 2,369) or Negative (n = 3,820) for TgAb and/or TPOAb.

<p>Statistical analysis was performed on all patients excluding those with TSHRAb. 95% CI, 95% confidence interval.</p><p>Prevalence of Extra-Thyroidal Malignancies in Patients Positive (n = 2,369) or Negative (n = 3,820) for TgAb and/or TPOAb.</p

Odd ratio of various primary extra-thyroidal malignancies at different ages in 6,389 female patients affected by benign or malignant thyroid diseases.

<p>Odd ratio of various primary extra-thyroidal malignancies at different ages in 6,389 female patients affected by benign or malignant thyroid diseases.</p

Thyroid Diseases, Age and Extra-Thyroidal Malignancies in the 6,386 Female Patients Included in the Study.

<p>NNTD, non-nodular thyroid disease; SN, solitary nodule; MNTD, multinodular thyroid disease; DTC, differentiated thyroid cancer; n.d., not determinable; 95% CI, 95% confidence interval. The expected cases in the different patient groups were estimated according to the prevalence of the different tumors occurring in the general population.</p><p>Thyroid Diseases, Age and Extra-Thyroidal Malignancies in the 6,386 Female Patients Included in the Study.</p

Univariate statistical analysis of Aurora-A and Aurora-B expression and clinicopathological parameters in 87 PTC patients.

<p>Corr. Coeff.: correlation coefficient.</p><p>Univariate statistical analysis of Aurora-A and Aurora-B expression and clinicopathological parameters in 87 PTC patients.</p

Cox regression analysis of different variables with recurrences in PTC patients.

<p>Cox regression analysis of different variables with recurrences in PTC patients.</p

Expression of Aurora kinases in 87 papillary thyroid cancer tissues.

<p>A and B) Variations in the expression of Aurora-A and Aurora-B in papillary thyroid cancer tissues. The fold changes were calculated considering the Aurora-A or Aurora-B mRNAs levels observed in normal matched thyroid tissue equal to 1. The statistical evaluation of the data was performed usingthe non-parametric Mann-Whitney test. The small bars in the graph indicate the median values. C) Correlation analysis of Aurora-A and Aurora-B mRNAs in PTC tissues. The data were evaluated by applying the Rho Spearman test.</p