Abstract
BackgroundEDC1 is a novel type of antibody-drug conjugate which binds and inhibits the Na,K-ATPase on the surface of cancer cells expressing dysadherin. The purpose of this study was to determine the expression of dysadherin in different types of thyroid carcinoma, and evaluate the therapeutic potential of EDC1 for thyroid carcinomas.MethodsThyroid tissues from 158 patients were examined for dysadherin expression and correlation with clinicopathological features. Thyroid cancer cell lines were examined for the expression of dysadherin and effective dose range of EDC1.RESULTSOne in 53 benign thyroid tissues and 62% of thyroid cancers expressed dysadherin. All anaplastic and a majority of papillary thyroid cancers overexpressed dysadherin, while 25% of follicular thyroid cancers was found to be positive for dysadherin. Dysadherin expression significantly correlated with extrathyroidal extension and lymph node metastases in papillary thyroid cancer. Five of six human thyroid cancer cell lines analyzed expressed high levels of dysadherin. Of those cells lines sensitive to EDC1, half maximal effective concentrations (EC50) were observed to be between 0.125 nM and 1 nM.ConclusionsEDC1 showed selective inhibition of growth in thyroid cancer cells with moderate to high expression of dysadherin, thus could be a specific and effective treatment.
Highlights
Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S [1]
Dysadherin expression significantly correlated with extrathyroidal extension and lymph node metastases in papillary thyroid cancer
While generally thyroid cancers are highly curable with the recommended treatment of thyroidectomy and radioactive iodine ablation [2], anaplastic thyroid cancer (ATC) and about 20% of welldifferentiated thyroid cancers present a more aggressive phenotype of distant metastasis or recurrence associated with increased mortality [3,4,5,6]
Summary
Thyroid cancer is the most common endocrine malignancy and the most rapidly increasing cancer in the U.S [1]. While generally thyroid cancers are highly curable with the recommended treatment of thyroidectomy and radioactive iodine ablation [2], anaplastic thyroid cancer (ATC) and about 20% of welldifferentiated thyroid cancers present a more aggressive phenotype of distant metastasis or recurrence associated with increased mortality [3,4,5,6]. Many of these aggressive thyroid cancers do not concentrate radioactive iodide from the lack of the sodium/iodide symporter (SLC5A5) [7, 8, 9], resulting in decreased survival [8, 10]. The purpose of this study was to determine the expression of dysadherin in different types of thyroid carcinoma, and evaluate the therapeutic potential of EDC1 for thyroid carcinomas
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