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Potencial da 2-deoxy-D-glucose como agente terapêutico no melanoma - revisão sistemática
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Abstract(s)
O melanoma maligno é um cancro agressivo e, por esse motivo, apresenta uma grande tendência para ocorrência de metástases na fase inicial da doença. Neste caso, as opções de tratamento são limitadas e existe ainda uma grande necessidade de desenvolver estratégias adicionais para otimizar a resposta terapêutica, tais como a descoberta de novos fármacos ou redirecionamento de moléculas já existentes. Segundo o “Efeito Warburg”, as células cancerígenas, mesmo em condições aeróbias, preferem o metabolismo glicolítico para produção de ATP, ao invés da via da fosforilação oxidativa. Uma vez que, a molécula 2-deoxy-D-glucose é um análogo da glucose com potencial na inibição da glicólise, sendo capaz de conduzir as células cancerígenas à apoptose, quando isolada ou em combinação, esta molécula representa um promissor agente anticancerígeno.
O foco desta monografia foi avaliar o potencial terapêutico da molécula 2-deoxy-D-glucose no tratamento do melanoma, elaborando a primeira revisão sistemática que teve como principal objetivo a recolha e análise de toda a informação existente acerca deste tema. Em primeiro lugar foi estabelecida a questão de investigação e elaborado o protocolo de investigação onde foram definidos os critérios de inclusão e exclusão, os termos de pesquisa e as bases de dados a utilizar. Foram incluídos 17 estudos publicados entre 1998 e 2019. A 2-deoxy-D-glucose demonstrou aumentar principalmente o stress do retículo endoplasmático e autofagia e inibir a glicólise, proliferação, migração e invasão celular, bem como diminuir a viabilidade celular. Foi capaz de potenciar o efeito dos agentes terapêuticos N-dodecilimidazol, cisplatina, imiquimod, TRAIL, coronatina e metiljasmonato.
A 2-deoxy-D-glucose apresenta potencial anticancerígeno, no entanto a sua combinação com outros agentes terapêuticos contribui para um maior sucesso no tratamento do melanoma.
The malignant melanoma is an aggressive cancer and, for that reason,has a huge tendency to occur metastasis in the initial fase of the disease. In this case, the treatment options are limited and still exists an huge necessity to develop additional strategies in order to optimize the therapeutic response, such as the discovery of new drugs or the redirection of pre-existing molecules. According to the “Warburg Effect”, cancer cells, even under aerobic conditions, prefer glycolytic metabolism for the production of ATP, instead the oxidative phosphorylation route. Once that the 2-deoxy-D-glucose molecule is a glucose analogue with the potential to inhibit glycolysis, by being able to lead the cancer cells to apoptosis, when isolated or in combination, this molecule represents a promising anticancer agent. The main focus of this monograph was to evaluate the therapeutic potencial of the 2-deoxy-D-glucose molecule in the melanoma treatment, by elaborating the first systematic revision that had as main goal gathering and analyzing all the information that exists about this subject. Firstly, it was established the investigation question and elaborated the investigation protocole where it was defined the inclusion and exclusion criteria, the research terms and the used data bases. Were included 17 studies published between 1998 and 2019. The 2-deoxy-D-glucose has been shown to increase mainly the endoplasmic reticulum stress and autophagy and to inhibit glycolysis, proliferation, migration and cell invasion, as well as to decrease cell viability. It was possible to potentiate the effects of the therapeutic agents N-dodecylimidazole, cisplatin, imiquimod, TRAIL, coronatin and methyljasmonate. The 2-deoxy-D-glucose presents anti-cancer potential, however its combination with other therapeutic agents contributes to a bigger success in the melanoma treatment. Key words: 2-deoxy-D-glucose, melanoma, glycolysis inhibition, therapeutic combination.
The malignant melanoma is an aggressive cancer and, for that reason,has a huge tendency to occur metastasis in the initial fase of the disease. In this case, the treatment options are limited and still exists an huge necessity to develop additional strategies in order to optimize the therapeutic response, such as the discovery of new drugs or the redirection of pre-existing molecules. According to the “Warburg Effect”, cancer cells, even under aerobic conditions, prefer glycolytic metabolism for the production of ATP, instead the oxidative phosphorylation route. Once that the 2-deoxy-D-glucose molecule is a glucose analogue with the potential to inhibit glycolysis, by being able to lead the cancer cells to apoptosis, when isolated or in combination, this molecule represents a promising anticancer agent. The main focus of this monograph was to evaluate the therapeutic potencial of the 2-deoxy-D-glucose molecule in the melanoma treatment, by elaborating the first systematic revision that had as main goal gathering and analyzing all the information that exists about this subject. Firstly, it was established the investigation question and elaborated the investigation protocole where it was defined the inclusion and exclusion criteria, the research terms and the used data bases. Were included 17 studies published between 1998 and 2019. The 2-deoxy-D-glucose has been shown to increase mainly the endoplasmic reticulum stress and autophagy and to inhibit glycolysis, proliferation, migration and cell invasion, as well as to decrease cell viability. It was possible to potentiate the effects of the therapeutic agents N-dodecylimidazole, cisplatin, imiquimod, TRAIL, coronatin and methyljasmonate. The 2-deoxy-D-glucose presents anti-cancer potential, however its combination with other therapeutic agents contributes to a bigger success in the melanoma treatment. Key words: 2-deoxy-D-glucose, melanoma, glycolysis inhibition, therapeutic combination.
Description
Keywords
2-deoxy-D-glucose Melanoma Inibição da glicólise Combinação Terapêuticao