New perspectives on the treatment of differentiated thyroid cancer

Abstract

Even though differentiated thyroid carcinoma is a slow growing and usually curable disease, recurrence occurs in 20-40% and cellular dedifferentiation in up to 5% of cases. Conventional chemotherapy and radiotherapy have just a modest effect on advanced thyroid cancer. Therefore, dedifferentiated thyroid cancer represents a therapeutic dilemma and a critical area of research. Targeted therapy, a new generation of anticancer treatment, is planned to interfere with a specific molecular target, typically a protein that is believed to have a critical role in tumor growth or progression. Since many of the tumor-initiation events have already been identified in thyroid carcinogenesis, targeted therapy is a promising therapeutic tool for advanced thyroid cancer. Several new drugs are currently being tested in in vitro and in vivo studies and some of them are already being used in clinical trials, like small molecule tyrosine kinase inhibitors. In this review, we discuss the bases of targeted therapies, the principal drugs already tested and also options of redifferentiation therapy for thyroid carcinoma. Apesar de o carcinoma diferenciado da tireóide ser considerado uma doença de curso indolente e geralmente curável, recorrência tumoral ocorre em aproximadamente 20 a 40% e desdiferenciação celular, em até 5% dos casos. A quimioterapia convencional e a radioterapia apresentam apenas um modesto efeito sobre o câncer de tireóide avançado. Dessa forma, o carcinoma da tireóide desdiferenciado representa um dilema terapêutico e uma importante área de pesquisa. A terapia direcionada, uma nova geração de tratamento para o câncer, tem como objetivo interferir com um alvo molecular específico, geralmente uma proteína considerada fundamental para o crescimento e progressão tumoral. Como muitos eventos iniciadores do processo de carcinogênese tireoideana já foram identificados, a terapia direcionada representa uma promissora opção terapêutica para o carcinoma da tireóide avançado. Várias drogas novas estão em estudos in vitro e in vivo e algumas já estão sendo testadas em estudos clínicos, como as pequenas moléculas inibidoras de tirosina cinase. Nesta revisão, as bases moleculares da terapia direcionada, as principais drogas utilizadas e as opções terapêuticas de rediferenciação do carcinoma da tireóide serão discutidas.

Partial remission of metastatic papillary thyroid carcinoma with sunitinib. Report of a case and review of the literature

“…In the last few years, several clinical trials using tyrosine kinase inhibitors for the treatment of progressive thyroid cancer have been initiated [25][26][27]. Sunitinib, SU11248, is a derivative of indolinone and has a wide spectrum of inhibitory actions on tyrosine kinases [28].…”

Flavonoids, Thyroid Iodide Uptake and Thyroid Cancer—A Review

“…Even though differentiated thyroid carcinoma is often a painless and curable disease, the cellular dedifferentiation can occur in about 5% of cases [78]. The cellular dedifferentiation can be a consequence of epithelial-mesenchymal transition (EMT), characterized by multiple biochemical and morphological changes enabling polarized epithelial cells to assume a mesenchymal phenotype, increasing proliferation, migration and invasiveness abilities, besides resistance to apoptosis [79,80].…”

Anaplastic thyroid cancer – an overview of genetic variations and treatment modalities

“…There have been several trials evaluating strategies to redifferentiate radioiodine-resistant well differentiated thyroid cancers in an attempt to render these tumors responsive to this treatment modality. 75,76 A recent study by Ho et al 77 successfully used selumetinib, a selective allosteric MEK1 and MEK2 inhibitor as a means to reestablish radioiodine avidity in non-iodine avid advanced papillary thyroid cancer. The activation of the MAPK or MEK is thought to play a critical role in the pathogenesis of radioiodine resistance.…”