ECE2010 Poster Presentations Thyroid (122 abstracts)
Panobinostat restores iodine uptake in primary cultures of undifferentiated thyroid tumours
Maria Graziella Catalano 1 , Mariateresa Pugliese 1 , Antonina Germano 1 , Roberta Poli 1 , Nicola Palestini 2 , Franco Mainini 3 , Nicoletta Fortunati 4 & Giuseppe Boccuzzi 1,
1Department of Clinical Pathophysiology, University of Torino, Torino, Italy; 2Department of Surgery, University of Torino, Torino, Italy; 3Novartis Farma S.p.A., Origgio, Italy; 4Oncological Endocrinology, AOU San Giovanni Battista, Torino, Italy.
A functional sodium iodide symporter (NIS) is essential for radioiodine treatment of thyroid cancer. Unfortunately, most of de-differentiated tumours as well as anaplastic thyroid cancers loss the ability to concentrate iodine. Loss of NIS expression usually depends on epigenetic modifications, suggesting the use of epigenetic drugs as promising tools for re-differentiation. Panobinostat (LBH589) is a novel deacetylase inhibitor, acting at nanomolar concentrations, currently in phase I–II clinical evaluation for its anti-tumour activity in advanced refractory solid tumours and hematologic malignancies. The aim of the present work was to define the pro-differentiating activity of LBH589 with particular regards to NIS expression and function in both immortalized cell lines as well as in primary cultures. To this aim, two different immortalized anaplastic thyroid cancer cell lines (BHT-101 and CAL-62) and four primary cultures derived from patients who underwent thyroidectomy for undifferentiated thyroid cancers (1 sternal metastasis from a recurrent PDTC, and 3 ATC), were treated with LBH589 (5–100 nM). LBH589 induced NIS mRNA expression in BHT-101 and CAL-62 cells in a dose dependent manner and in all the four primary cultures, as revealed by RT-Real-Time PCR. Immunofluorescence microscopy clearly demonstrated the presence of NIS protein in all the cell cultures. Finally, 125I uptake was performed and demonstrated that LBH589 resulted in a significant up-take of iodide in thyroid cancer cells.
In conclusion, data from our study on both immortalized and primary cultures strongly suggest that LBH589 is a very good candidate for carefully designed clinical trials aimed at restoring iodide uptake in patients with undifferentiated thyroid cancer. Moreover, the novelty of testing the drug on primary cultures could allow an increase in the effectiveness of the treatment in single patients.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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