Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFRGS |
Texto Completo: | http://hdl.handle.net/10183/215125 |
Resumo: | Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies. |
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Ceolin, LucieliDuval, Marta Amaro da SilveiraBenini, Antônio FelippeVargas, Carla Vaz FerreiraMaia, Ana Luiza Silva2020-11-18T04:10:38Z20191479-6821http://hdl.handle.net/10183/215125001118213Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies.application/pdfengEndocrine-related cancer [recurso eletrônico]. [Amsterdam]. Vol. 26, no. 9 (2019), p. R499–R518Neoplasias da glândula tireóideInibidores de proteínas quinasesTerapia de alvo molecularImunoterapiaMedullary thyroid cancerTyrosine kinase inhibitorMolecular target therapyMedullary thyroid carcinoma beyond surgery : advances, challenges, and perspectivesEstrangeiroinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRGSinstname:Universidade Federal do Rio Grande do Sul (UFRGS)instacron:UFRGSTEXT001118213.pdf.txt001118213.pdf.txtExtracted Texttext/plain118073http://www.lume.ufrgs.br/bitstream/10183/215125/2/001118213.pdf.txta6a74f3bf4d784e48513c8a03dee569fMD52ORIGINAL001118213.pdfTexto completo (inglês)application/pdf1600883http://www.lume.ufrgs.br/bitstream/10183/215125/1/001118213.pdfc59b424cab5f985ca5daac9905ee4836MD5110183/2151252020-11-19 05:15:06.573961oai:www.lume.ufrgs.br:10183/215125Repositório de PublicaçõesPUBhttps://lume.ufrgs.br/oai/requestopendoar:2020-11-19T07:15:06Repositório Institucional da UFRGS - Universidade Federal do Rio Grande do Sul (UFRGS)false |
dc.title.pt_BR.fl_str_mv |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
title |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
spellingShingle |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives Ceolin, Lucieli Neoplasias da glândula tireóide Inibidores de proteínas quinases Terapia de alvo molecular Imunoterapia Medullary thyroid cancer Tyrosine kinase inhibitor Molecular target therapy |
title_short |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
title_full |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
title_fullStr |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
title_full_unstemmed |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
title_sort |
Medullary thyroid carcinoma beyond surgery : advances, challenges, and perspectives |
author |
Ceolin, Lucieli |
author_facet |
Ceolin, Lucieli Duval, Marta Amaro da Silveira Benini, Antônio Felippe Vargas, Carla Vaz Ferreira Maia, Ana Luiza Silva |
author_role |
author |
author2 |
Duval, Marta Amaro da Silveira Benini, Antônio Felippe Vargas, Carla Vaz Ferreira Maia, Ana Luiza Silva |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Ceolin, Lucieli Duval, Marta Amaro da Silveira Benini, Antônio Felippe Vargas, Carla Vaz Ferreira Maia, Ana Luiza Silva |
dc.subject.por.fl_str_mv |
Neoplasias da glândula tireóide Inibidores de proteínas quinases Terapia de alvo molecular Imunoterapia |
topic |
Neoplasias da glândula tireóide Inibidores de proteínas quinases Terapia de alvo molecular Imunoterapia Medullary thyroid cancer Tyrosine kinase inhibitor Molecular target therapy |
dc.subject.eng.fl_str_mv |
Medullary thyroid cancer Tyrosine kinase inhibitor Molecular target therapy |
description |
Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2–4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019 |
dc.date.accessioned.fl_str_mv |
2020-11-18T04:10:38Z |
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Estrangeiro info:eu-repo/semantics/article |
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http://hdl.handle.net/10183/215125 |
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1479-6821 |
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001118213 |
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http://hdl.handle.net/10183/215125 |
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eng |
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dc.relation.ispartof.pt_BR.fl_str_mv |
Endocrine-related cancer [recurso eletrônico]. [Amsterdam]. Vol. 26, no. 9 (2019), p. R499–R518 |
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info:eu-repo/semantics/openAccess |
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