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Viroterapia oncolítica : vírus como agentes terapêuticos do cancro
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Resumo(s)
O cancro é um grupo de doenças bastante alargado e heterogéneo que afeta cada vez mais a esperança de vida a nível mundial. Em 2020 foi causa de morte de 10 milhões de pessoas em todo o mundo, sendo o cancro mais mortal o do pulmão e o mais incidente o da mama. A erradicação deste problema de saúde pública tem sido de difícil resolução. Apesar de todas as terapêuticas já existentes, continuam a permanecer algumas lacunas que podem ser ultrapassadas com o auxílio da viroterapia oncolítica.
Os vírus oncolíticos (OVs), pensados inicialmente para uma ação de lise tumoral direta, são agora direcionados para uma perspetiva de estimulação do sistema imunitário e combinação com terapêuticas já existentes. Esta ação indireta é capaz de estimular tanto o sistema imunitário inato, como o adaptativo, já que possuem ação nas diferentes etapas da resposta anti-tumoral. Assim, os mecanismos de fuga ao sistema imunitário existentes no microambiente tumoral podem ser ultrapassados. A especificidade tumoral dos OVs é conseguida através de diferenças genéticas das células tumorais (vias anti-virais comprometidas), tal como através de alterações genéticas feitas no próprio vírus.
A importância do conhecimento estrutural de cada vírus e da sua interação com os recetores tumorais é evidente. Só assim é possível delinear uma terapêutica direcionada com o máximo de eficácia e o mínimo de toxicidade.
A combinação terapêutica com OVs tem sido estudada e demonstrado bons resultados. Esta combinação tem sido realizada com quimioterapia, radioterapia, terapêuticas dirigidas e imunoterapia. Mais recentemente têm-se pensado nos OVs como vetores para a libertação seletiva de micro RNAs (miRNAs) anti-tumorais.
Atualmente estão 155 ensaios clínicos em vigor, em recrutamento ou não, com a premissa da utilização de OVs.
Cancer is a large and diverse group of diseases that is increasingly affecting life expectancy worldwide. In the year of 2020, it caused 10 million deaths, with lung and breast cancer being the most deadly and common cancers, respectively. The eradication of this public health problem has been of rather difficult solution. Despite all the existing therapies, there are still some gaps that can be overcome with the help of Oncolytic Virotherapy. The Oncolytic Viruses (OVs), initially conceived for direct tumor lysis, are now being used in combination with existing therapies to stimulate the immune system. This indirect action is capable of stimulating both the innate and adaptive immune systems, as they act at different stages of the anti-tumoral response. Thus, the immune system escape mechanisms present on the tumoral microenvironment can be overcome. The tumor specificity of OVs is achieved through the genetic differences in tumor cells (compromised antiviral signaling), and by genetic modifications on the virus itself. Knowledge of the structure of each virus and its interaction with tumoral receptors is clearly important. This is the only way to plan a targeted therapy with maximum efficacy and minimum toxicity. The therapeutic combination with OVs has been studied and has shown good results. It has been done in combination with chemotherapy, radiotherapy, directed therapeutics and immunotherapy. Recently OVs have been considered as vectors for selective release of anti-tumoral micro-RNA (miRNAs). Currently there are 155 ongoing clinical trials, in recruitment or otherwise, with the idea of OVs as therapeutic agents.
Cancer is a large and diverse group of diseases that is increasingly affecting life expectancy worldwide. In the year of 2020, it caused 10 million deaths, with lung and breast cancer being the most deadly and common cancers, respectively. The eradication of this public health problem has been of rather difficult solution. Despite all the existing therapies, there are still some gaps that can be overcome with the help of Oncolytic Virotherapy. The Oncolytic Viruses (OVs), initially conceived for direct tumor lysis, are now being used in combination with existing therapies to stimulate the immune system. This indirect action is capable of stimulating both the innate and adaptive immune systems, as they act at different stages of the anti-tumoral response. Thus, the immune system escape mechanisms present on the tumoral microenvironment can be overcome. The tumor specificity of OVs is achieved through the genetic differences in tumor cells (compromised antiviral signaling), and by genetic modifications on the virus itself. Knowledge of the structure of each virus and its interaction with tumoral receptors is clearly important. This is the only way to plan a targeted therapy with maximum efficacy and minimum toxicity. The therapeutic combination with OVs has been studied and has shown good results. It has been done in combination with chemotherapy, radiotherapy, directed therapeutics and immunotherapy. Recently OVs have been considered as vectors for selective release of anti-tumoral micro-RNA (miRNAs). Currently there are 155 ongoing clinical trials, in recruitment or otherwise, with the idea of OVs as therapeutic agents.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Viroterapia oncolítica Vírus Oncologia Imunoterapia Mestrado Integrado - 2023