Ácido retinóico: uma terapia promissora para carcinoma treoideano desdiferenciado?

For most differentiated thyroid carcinomas, as papillary and follicular carcinomas, following total thyroidectomy and 131I therapy for thyroid remnant ablation, treatment with thyroid hormones to suppress TSH levels will reduce the growth of any remaining thyroid cancer cells, and thyroid cell-specific radiation therapy will either cure or control the disease. Thyroid carcinomas are considered poorly differentiated when they start to lose such functions as iodine uptake and thyrotropin-dependence for growth and production of thyroid proteins like NIS, thyroglobulin and desiodases. One of the greatest challenges in the management of patients with follicular cell-derived thyroid cancer is the treatment of tumors that progressed despite surgery, (131)I and T4 suppression of TSH. With the better knowledge of the abnormal molecular signaling in thyroid cancer cells, actually known targeted cancer therapies, directed against molecules involved in neoplastic transformation, are being used. As the critical molecular requirements for tumor initiation, maintenance and progression are identified, combination therapies with targeted agents acting on each of them will improve the treatment of poorly differentiated thyroid carcinoma.

Section: áCido Retinóicounclassified

Carcinoma de tireóide pouco diferenciado: novas considerações terapêuticas

Graf

2005

“…O ácido retinóico (AR) tem sido usado em pacientes com metástases não iodocaptantes na tentativa de rediferenciação tumoral. Além de aumentar a expressão do NIS e a captação de iodo, o AR também aumenta a apoptose (36), reduz a sÌntese de DNA (36) e o poder de invasão das células tumorais (37). Clinicamente, aumento da captação de iodo-131 (38)(39)(40)(41), redução da Tg sérica (38,39,41) e estabilização ou redução tumoral (40,41) têm sido demonstrados com uso do AR em pacientes com carcinoma de tireóide.…”

Section: Tratamento De Pacientes Com Metástases Não Iodocaptantes Na ...unclassified

“…Clinicamente, aumento da captação de iodo-131 (38)(39)(40)(41), redução da Tg sérica (38,39,41) e estabilização ou redução tumoral (40,41) têm sido demonstrados com uso do AR em pacientes com carcinoma de tireóide. Estes estudos também confirmam a segurança desta terapia, sendo os efeitos adversos reversÌveis; e ressecamento da pele e mucosas e hipertrigliceridemia são os mais freqüentes (37,(40)(41)(42)(43). Apesar da resposta não ser superior a outras formas de tratamento, quando parâmetros além do aumento da captação de iodo-131 são considerados, os resultados promissores e a segurança desta terapia fazem do AR uma opção terapêutica em pacientes com tumores desdiferenciados (37).…”

Section: Tratamento De Pacientes Com Metástases Não Iodocaptantes Na ...unclassified

“…Estes estudos também confirmam a segurança desta terapia, sendo os efeitos adversos reversÌveis; e ressecamento da pele e mucosas e hipertrigliceridemia são os mais freqüentes (37,(40)(41)(42)(43). Apesar da resposta não ser superior a outras formas de tratamento, quando parâmetros além do aumento da captação de iodo-131 são considerados, os resultados promissores e a segurança desta terapia fazem do AR uma opção terapêutica em pacientes com tumores desdiferenciados (37). Um maior conhecimento das diferentes isoformas dos receptores do AR permitirá uma predição mais precisa da resposta a este tratamento (36,44).…”

Section: Tratamento De Pacientes Com Metástases Não Iodocaptantes Na ...unclassified

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Abordagem dos pacientes com carcinoma diferenciado de tireóide com tireoglobulina sérica elevada e pesquisa de corpo inteiro negativa

Rosário

Maia

Barroso

et al. 2005

Findings of elevated thyroglobulin (Tg) and a negative whole-body scan (WBS) are not uncommon during the follow-up of differentiated thyroid carcinoma. In 12% of our patients submitted to thyroidectomy and radioiodine with Tg >10 ng/ml during hypothyroidism had a negative diagnostic WBS. This finding generally corresponds to a false-negative WBS. Inadequate preparation in terms of iodine exposure and insufficient elevation of TSH should be excluded. Micrometastases which do not accumulate sufficient iodine to be detected by low radioiodine activity and the loss of the capacity to express the sodium/iodine symporter explain many cases. In patients with elevated Tg, metastases can be identified after the administration of a therapeutic radioiodine dose, with this procedure being indicated in cases with Tg >10 ng/ml during hypothyroidism or >5 ng/ml after recombinant TSH, after exclusion of lung and cervical macrometastases. In the present study, 5 of 7 patients with these criteria showed ectopic uptake on post-therapy WBS. If the post-therapy scan is negative or reveals discrete uptake in the thyroid bed, other methods (e.g. FDG PET) can be performed, and the physician should not insist on radioiodine therapy. If WBS detect lymph node metastases, surgery is indicated, while in cases of diffuse lung metastases radioiodine is indicated until the occurrence of a negative WBS or normalization of stimulated Tg levels. Patients with a positive post-therapy scan may show a significant reduction in Tg, with even complete remission in some cases after radioiodine, but the impact of this treatment on mortality remains controversial.

Câncer diferenciado da tiróide: fatores prognósticos e tratamento

Ward

Assumpção²

2004

Because most differentiated thyroid carcinomas have an excellent prognosis, some authors have claimed that these patients are suffering from over treatment. Grouping patient- and tumor-specific factors have been proposed for prognostic stratification, but no clinicopathologic staging was demonstrated to be useful at the present time. More recently, molecular genetic tools have been used to identify and understand how the primary tumor progresses and many molecular markers have been proposed in order to distinguish the subset of patients at risk of developing metastasis. Here we analyzed some of them, with emphasis on the expression of NIS, a determinant of prognosis since the functional integrity of the iodine transport is essential to assure an uptake of radioiodine high enough to detect and destroy any tumoral thyroid tissue. More recent observations on how some relevant molecular genetics aspects of thyroid cancer impact new potential therapeutic approaches are also discussed.