Dysadherin specific drug conjugates for the treatment of thyroid cancers with aggressive phenotypes.
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.
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Surgery, University of Alabama Birmingham School of Medicine, Birmingham, AL, USA.
Samuel
S
Jang
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Xiao-Min
XM
Yu
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Celina
C
Montemayor-Garcia
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Kamal
K
Ahmed
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Eric
E
Weinlander
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Ricardo V
RV
Lloyd
Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Ajitha
A
Dammalapati
Centrose LLC, Madison, WI, USA.
David
D
Marshall
Centrose LLC, Madison, WI, USA.
James R
JR
Prudent
Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.|Department of Surgery, University of Alabama Birmingham School of Medicine, Birmingham, AL, USA.
Herbert
H
Chen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007473:Ion Channels; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008840:Microfilament Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D010641:Phenotype; D013964:Thyroid Neoplasms / Q000188:drug therapy*; D055815:Young Adult
C451410:FXYD5 protein, human; D007473:Ion Channels; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; D009363:Neoplasm Proteins
aggressive phenotype; antibody-drug conjugate; dysadherin; thyroid cancer; treatment