Work

Dysadherin specific drug conjugates for the treatment of thyroid cancers with aggressive phenotypes

Year: 2017

Type: article

Abstract: // Samuel Jang 1, 2 , Xiao-Min Yu 1 , Celina Montemayor-Garcia 3 , Kamal Ahmed 1 , Eric Weinlander 1 , Ricardo V. Lloyd 3 , Ajitha Dammalapati 3 , David Marshall 4 , James R. Prudent 4 , Herbert Chen 1, 2 1 Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA 2 Department of Surgery, University of Alabama Birmingham School of Medicine, Birmingham, AL, USA 3 Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA 4 Centrose LLC, Madison, WI, USA Correspondence to: Herbert Chen, email: [email protected] Keywords: thyroid cancer, dysadherin, antibody-drug conjugate, aggressive phenotype, treatment Received: October 04, 2016 Accepted: January 08, 2017 Published: January 30, 2017 ABSTRACT Background : EDC1 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. Methods: Thyroid 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. Results: One 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. Conclusions : EDC1 showed selective inhibition of growth in thyroid cancer cells with moderate to high expression of dysadherin, thus could be a specific and effective treatment.

Source: Oncotarget

DOI: 10.18632/oncotarget.14904