Effects of panobinostat, a novel deacetylase inhibitor, in primary cultures of anaplastic thyroid tumors.

Abstract

e13625 Background: Anaplastic thyroid tumors (ATC) are aggressive human cancers that are resistant to conventional therapy. Panobinostat (LBH589) is a novel deacetylase inhibitor, acting at nanomolar concentrations, currently in phase I-II clinical evaluation for its anti-tumor activity in advanced refractory solid tumors and hematologic malignancies. Aims of the present work were to evaluate the cytotoxic and pro-differentiating activities of LBH589 on primary cultures derived from patients who underwent thyroidectomy for undifferentiated thyroid cancers. Methods: To these aims, we treated four primary cultures (1 sternal metastasis from a recurrent PDTC, and 3 ATC) with LBH589 (5-200nM). After treatment, we evaluated: 1) cell viability and cytotoxicity by WST-1 method; 2) mRNA NIS expression by RT-real-time PCR; 3) presence of NIS protein by indirect immunofluorescence; 3) ability of primary cultures to concentrate iodine by a I125 uptake. Results: At nanomolar concentrations, LBH589 treatment resulted in impairment of cell viability; induction of NIS mRNA and protein; up-take of iodide in all the primary cultures. Conclusions: In conclusion, data from our study on primary cultures strongly suggest that LBH589 is a very good candidate for carefully designed clinical trials for the treatment of this kind of cancer which is known not to respond to conventional therapy. Moreover, the novelty of testing the drug on primary cultures could allow an increase in the effectiveness of the treatment in single patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis