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Mecanismos de oncogénese viral
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Segundo a Organização Mundial da Saúde, o cancro é a primeira ou segunda principal causa de morte antes dos 70 anos, representando um grande problema de saúde pública a nível mundial. A possibilidade de que o cancro poderia ter uma etiologia infeciosa foi identificada no início do século XX, mas só anos mais tarde, em 1964, foi estabelecida uma relação entre o aparecimento de cancro e as infeções virais aquando da deteção de partículas virais em células tumorais derivadas do Linfoma de Burkitt. Atualmente, sete vírus são classificados como vírus oncogénicos humanos, nomeadamente, Vírus Epstein-Barr, Vírus do Papiloma Humano, Vírus da Hepatite B, Vírus da Hepatite C, Herpesvírus associado ao Sarcoma de Kaposi, Vírus Linfotrópico de células T Humanas do Tipo 1 e Poliomavírus das Células de Merkel. A oncogénese viral consiste num processo complexo que compreende inúmeros eventos genéticos induzidos pelos vírus oncogénicos, os quais possuem capacidade de modular diversas vias de transdução de sinal, tais como Pi3K-AKT-mTOR, MAPK, NOTCH, WNT/β-catenina, NF-κB e resposta a danos no DNA. A interferência destas vias pode dever-se às proteínas oncogénicas específicas de cada vírus (mecanismo direto) ou ser resultado da inflamação crónica provocada pela libertação de citocinas, quimiocinas e espécies reativas de oxigénio (mecanismo indireto). Existe ainda a teoria “Hit-and-Run”, a qual sugere que os vírus oncogénicos desencadeiam a formação de cancro após a acumulação de inúmeras mutações por parte das células hospedeiras, mesmo que o genoma viral seja, entretanto, totalmente perdido. Apesar de haver evidências que suportem esta hipótese, são necessários mais estudos que a possam comprovar. De entre todos os vírus oncogénicos humanos, destacam-se o vírus Epstein Barr, vírus do Papiloma Humano, vírus da Hepatite B e vírus da Hepatite C, visto que apresentam uma maior prevalência a nível global. Deste modo, serão aprofundados os respetivos mecanismos oncogénicos envolvendo as vias de sinalização referidas anteriormente, assim como as abordagens terapêuticas e perspetivas futuras.
According to the World Health Organization, cancer is the first or second leading cause of death before the age of 70, representing a major public health problem worldwide. The possibility that cancer could have an infectious etiology was identified at the beginning of the 20th century, but it wasn't until years later, in 1964, that a link between the appearance of cancer and viral infections was established when viral particles were detected in tumor cells derived from Burkitt's Lymphoma. Currently, seven viruses are classified as human oncogenic viruses, namely Epstein-Barr Virus, Human Papilloma Virus, Hepatitis B Virus, Hepatitis C Virus, Kaposi's Sarcoma associated Herpesvirus, Human T-cell Lymphotropic Virus Type 1 and Merkel Cell Polyomavirus. Viral oncogenesis is a complex process comprising numerous genetic events induced by oncogenic viruses, which have the ability to modulate various signal transduction pathways, such as Pi3K-AKT-mTOR, MAPK, NOTCH, WNT/β-catenin, NF-κB and DNA damage response. The interference of these pathways may be due to the specific oncogenic proteins of each virus (direct mechanism) or be the result of chronic inflammation caused by the release of cytokines, chemokines and reactive oxygen species (indirect mechanism). There is also the "Hit-and-Run" theory, which suggests that oncogenic viruses trigger the formation of cancer after the accumulation of numerous mutations by the host cells, even if the viral genome is completely lost in the meantime. Although there is evidence to support this hypothesis, more studies are needed to prove it. Of all the human oncogenic viruses, Epstein-Barr virus, Human Papilloma virus, Hepatitis B virus and Hepatitis C virus stand out, as they have a higher prevalence globally. Therefore, the respective oncogenic mechanisms involving the signaling pathways mentioned above will be explored in depth, as well as therapeutic approaches and future prospects.
According to the World Health Organization, cancer is the first or second leading cause of death before the age of 70, representing a major public health problem worldwide. The possibility that cancer could have an infectious etiology was identified at the beginning of the 20th century, but it wasn't until years later, in 1964, that a link between the appearance of cancer and viral infections was established when viral particles were detected in tumor cells derived from Burkitt's Lymphoma. Currently, seven viruses are classified as human oncogenic viruses, namely Epstein-Barr Virus, Human Papilloma Virus, Hepatitis B Virus, Hepatitis C Virus, Kaposi's Sarcoma associated Herpesvirus, Human T-cell Lymphotropic Virus Type 1 and Merkel Cell Polyomavirus. Viral oncogenesis is a complex process comprising numerous genetic events induced by oncogenic viruses, which have the ability to modulate various signal transduction pathways, such as Pi3K-AKT-mTOR, MAPK, NOTCH, WNT/β-catenin, NF-κB and DNA damage response. The interference of these pathways may be due to the specific oncogenic proteins of each virus (direct mechanism) or be the result of chronic inflammation caused by the release of cytokines, chemokines and reactive oxygen species (indirect mechanism). There is also the "Hit-and-Run" theory, which suggests that oncogenic viruses trigger the formation of cancer after the accumulation of numerous mutations by the host cells, even if the viral genome is completely lost in the meantime. Although there is evidence to support this hypothesis, more studies are needed to prove it. Of all the human oncogenic viruses, Epstein-Barr virus, Human Papilloma virus, Hepatitis B virus and Hepatitis C virus stand out, as they have a higher prevalence globally. Therefore, the respective oncogenic mechanisms involving the signaling pathways mentioned above will be explored in depth, as well as therapeutic approaches and future prospects.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2023, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Oncogénese viral EBV HCV HBV HPV Mestrado Integrado - 2023