ECE2011 Poster Presentations Thyroid cancer (43 abstracts)
The effects of four different tyrosine kinase inhibitors on medullary and papillary thyroid cancer cells
H H G Verbeek 1, , M M Alves 2 , J W B deGroot 3 , J Osinga 2 , J T M Plukker 4 , T P Links 1 & R M W Hofstra 2
1Department of Endocrinology, University Medical Center Groningen, Groningen, The Netherlands; 2Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands; 3Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands; 4Department of Surgical Oncology, University Medical Center Groningen, Groningen, The Netherlands.
Introduction: Medullary and papillary thyroid carcinoma (MTC and PTC) are two types of thyroid cancer that can originate from activating mutations or rearrangements in the RET gene. Therapeutic options are limited in recurrent disease but since RET is a tyrosine kinase (TK) receptor involved in cellular growth and proliferation, treatment with a TK-inhibitor might be promising. Several TK-inhibitors have been tested in clinical trials, but it is unknown which inhibitor is most effective and if there is any specificity for particular RET mutations. We aimed to compare the effect of four TK inhibitors (axitinib, sunitinib, vandetanib and XL184) on cell proliferation, RET expression and autophosphorylation, and ERK activation in cell lines expressing a MEN2A (MTC-TT), a MEN2B (MZ-CRC-1) mutation, and a RET/PTC (TPC-1) rearrangement.
Design: Three cell lines, MTC-TT, MZ-CRC-1 and TPC-1 were cultured and treated with different concentrations of the four TK inhibitors. Effects on cell proliferation, RET and ERK expression and activation were determined.
Results: XL184 and vandetanib, most effectively inhibited cell proliferation, RET autophosphorylation in combination with a reduction of RET expression, and ERK phosphorylation in MTC-TT and MZ-CRC-1 respectively. TPC-1 cells showed a decrease in RET autophosphorylation after treatment with XL184, but no effect was observed on ERK activation.
Conclusion: There is indeed specificity for different RET mutations, with XL184 being the most potent inhibitor in MEN2A and PTC, and vandetanib the most effective in MEN2B in vitro. No TK inhibitor was superior for all the cell lines tested, indicating that mutation-specific therapies could be beneficial in treating MTC and PTC.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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