Loading...
Publication
Tiazolidinedionas como estratégia terapêutica no melanoma: revisão sistemática
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 2.17 MB | Adobe PDF |
Authors
Abstract(s)
O melanoma é uma doença mundial com incidência e mortalidade crescente, representando a forma mais agressiva de cancro da pele, e sendo responsável por 80% das mortes atribuídas a todas as neoplasias cutâneas. A resistência adquirida pelos doentes ao longo do tratamento constitui uma barreira ao sucesso da terapêutica, suscitando assim a necessidade de identificação de novos fármacos e novas opções terapêuticas. Além da potencial utilização da Metformina como fármaco anticancerígeno, surgem cada vez mais evidências de que as Tiazolidinedionas (TZDs), classe de fármacos antidiabéticos ligandos do recetor PPARγ, Recetor ativado de Proliferadores do Peroxisoma gama, podem ser igualmente eficazes para o tratamento do melanoma.
Esta monografia apresenta uma revisão sistemática acerca da potencial utilização das TZDs nesta patologia, o seu mecanismo de ação e vias envolvidas, e os resultados terapêuticos observados, visando identificar novas perspetivas de tratamento. Para o seu desenvolvimento, após formulação da questão de investigação, foi elaborado o protocolo de investigação com a definição dos termos de pesquisa (melanoma AND thiazolidinediones; rosiglitazone; pioglitazone; troglitazone; ciglitazone) e bases de dados (PubMed, Cochrane Library, Web of Science, B-on, ClinicalTrials.gov, RCAAP, e Open Grey) a utilizar. Após a pesquisa da literatura e seleção dos estudos através da aplicação dos critérios de inclusão e exclusão, a recolha e síntese dos dados, e interpretação dos resultados, incidiu sobre 24 estudos publicados entre 2002 e 2018.
Os resultados obtidos indicam que numa ampla variedade de células de melanoma, tanto de humanos como de ratinhos, as TZDs parecem diminuir a proliferação celular, induzir a apoptose, bem como a paragem do ciclo celular. Além disso, a regulação dos níveis de MITF (Fator de transcrição associado a microftalmia) pelas TZDs, fator importante que regula a transcrição dos genes envolvidos na síntese de melanina, parece estar implicada nos potenciais efeitos anticancerígenos. Deste modo, os resultados obtidos nesta revisão sistemática permitem sustentar a possibilidade da aplicação terapêutica das TZDs no melanoma.
Melanoma is a worldwide disease with increasing incidence and mortality, representing the most aggressive form of skin cancer, and accounting for 80% of deaths attributed to all skin cancers. Resistance acquired by patients throughout treatment is a barrier to successful therapy, thus raising the need for identification of new drugs and new therapeutic options. In addition to the potential use of metformin as an anticancer drug, there is increasing evidence that Thiazolidinediones (TZDs), a class of PPARγ (Peroxisome proliferator-activated receptor gama), receptor ligand antidiabetic drugs, may be equally effective for treating melanoma. This monograph presents a systematic review about the potential use of TZDs in this pathology, their mechanism of action and pathways involved, and the therapeutic results observed, aiming to identify new treatment perspectives. For its development, after formulating the research question, the research protocol was elaborated with the definition of the search terms (melanoma AND thiazolidinediones; rosiglitazone; pioglitazone; troglitazone; ciglitazone) and databases (PubMed, Cochrane Library, Web of Science, B-on, ClinicalTrials.gov, RCAAP, and Open Grey) to be used. After searching the literature and selecting studies by applying the inclusion and exclusion criteria, data collection and synthesis, and interpretation of results, focused on 24 studies published between 2002 and 2018. The results obtained indicate that in a wide variety of human and mouse melanoma cells, TZDs appear to decrease cell proliferation, induce apoptosis as well as cell cycle arrest. In addition, the regulation of MITF (microphtalmia-associated transcription factor) levels by TZDs, an important factor regulating the transcription of genes involved in melanin synthesis, appears to be implicated in potential anticancer effects. Thus, the results obtained in this systematic review support the possibility of therapeutic application of TZDs in melanoma.
Melanoma is a worldwide disease with increasing incidence and mortality, representing the most aggressive form of skin cancer, and accounting for 80% of deaths attributed to all skin cancers. Resistance acquired by patients throughout treatment is a barrier to successful therapy, thus raising the need for identification of new drugs and new therapeutic options. In addition to the potential use of metformin as an anticancer drug, there is increasing evidence that Thiazolidinediones (TZDs), a class of PPARγ (Peroxisome proliferator-activated receptor gama), receptor ligand antidiabetic drugs, may be equally effective for treating melanoma. This monograph presents a systematic review about the potential use of TZDs in this pathology, their mechanism of action and pathways involved, and the therapeutic results observed, aiming to identify new treatment perspectives. For its development, after formulating the research question, the research protocol was elaborated with the definition of the search terms (melanoma AND thiazolidinediones; rosiglitazone; pioglitazone; troglitazone; ciglitazone) and databases (PubMed, Cochrane Library, Web of Science, B-on, ClinicalTrials.gov, RCAAP, and Open Grey) to be used. After searching the literature and selecting studies by applying the inclusion and exclusion criteria, data collection and synthesis, and interpretation of results, focused on 24 studies published between 2002 and 2018. The results obtained indicate that in a wide variety of human and mouse melanoma cells, TZDs appear to decrease cell proliferation, induce apoptosis as well as cell cycle arrest. In addition, the regulation of MITF (microphtalmia-associated transcription factor) levels by TZDs, an important factor regulating the transcription of genes involved in melanin synthesis, appears to be implicated in potential anticancer effects. Thus, the results obtained in this systematic review support the possibility of therapeutic application of TZDs in melanoma.
Description
Keywords
Melanoma Tiazolidinedionas Proliferação celular Apoptose Paragem do ciclo celular