Abstract
Although well-differentiated thyroid carcinomas are usually curable by the combined effects of surgery, radioiodine ablation and thyroid stimulating hormone (TSH) suppressive therapy, recurrence develops in 20-40% of patients. During tumour progression, cellular de-differentiation occurs in up to 30% of cases and is usually accompanied by more aggressive growth, metastasis spread and loss of iodide uptake. The therapeutic options for de-differentiated thyroid cancer are limited and generally not efficient. Retinoic acids (RA) are biologically active metabolites of vitamin A that regulate growth and differentiation of many cell types, by binding to specific nuclear receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Recent studies have shown that RA can induce in vitro redifferentiation of thyroid carcinoma cell lines, as suggested by increased expression of the sodium/iodide symporter (NIS), type I iodothyronine deiodinase, alkaline phosphatase and by the increment of cellular 131I uptake. In addition to redifferentiating effects, RA also exert anti-proliferative actions, as the inhibition of mitosis and the induction of apoptosis. Previous clinical studies have shown that iodide uptake may be re-stimulated after RA in about 20-50% of patients with radioiodine non-responsive thyroid carcinoma. Longer follow-up of patients demonstrated that, besides iodide uptake increment, RA can induce tumour regression or at least tumour growth stabilisation. The therapy is generally well tolerated and the most frequent side effects are dryness of skin and mucosa, and hypertriglyceridemia. This paper describes the recent advances in the field of thyroid cancer therapy and reviews the use of RA as a promising novel therapeutic tool.
Keywords: differentiated thyroid carcinomas (dtc), thyroid stimulating hormone (tsh), vitamin a, sodium, nis
Current Pharmaceutical Design
Title: Tumour Re-Differentiation Effect of Retinoic Acid: A Novel Therapeutic Approach for Advanced Thyroid Cancer
Volume: 11 Issue: 19
Author(s): Sabrina M. Coelho, Mario Vaisman and Denise P. Carvalho
Affiliation:
Keywords: differentiated thyroid carcinomas (dtc), thyroid stimulating hormone (tsh), vitamin a, sodium, nis
Abstract: Although well-differentiated thyroid carcinomas are usually curable by the combined effects of surgery, radioiodine ablation and thyroid stimulating hormone (TSH) suppressive therapy, recurrence develops in 20-40% of patients. During tumour progression, cellular de-differentiation occurs in up to 30% of cases and is usually accompanied by more aggressive growth, metastasis spread and loss of iodide uptake. The therapeutic options for de-differentiated thyroid cancer are limited and generally not efficient. Retinoic acids (RA) are biologically active metabolites of vitamin A that regulate growth and differentiation of many cell types, by binding to specific nuclear receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Recent studies have shown that RA can induce in vitro redifferentiation of thyroid carcinoma cell lines, as suggested by increased expression of the sodium/iodide symporter (NIS), type I iodothyronine deiodinase, alkaline phosphatase and by the increment of cellular 131I uptake. In addition to redifferentiating effects, RA also exert anti-proliferative actions, as the inhibition of mitosis and the induction of apoptosis. Previous clinical studies have shown that iodide uptake may be re-stimulated after RA in about 20-50% of patients with radioiodine non-responsive thyroid carcinoma. Longer follow-up of patients demonstrated that, besides iodide uptake increment, RA can induce tumour regression or at least tumour growth stabilisation. The therapy is generally well tolerated and the most frequent side effects are dryness of skin and mucosa, and hypertriglyceridemia. This paper describes the recent advances in the field of thyroid cancer therapy and reviews the use of RA as a promising novel therapeutic tool.
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Cite this article as:
Coelho M. Sabrina, Vaisman Mario and Carvalho P. Denise, Tumour Re-Differentiation Effect of Retinoic Acid: A Novel Therapeutic Approach for Advanced Thyroid Cancer, Current Pharmaceutical Design 2005; 11 (19) . https://dx.doi.org/10.2174/1381612054367490
DOI https://dx.doi.org/10.2174/1381612054367490 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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