Atividade antitumoral de inibidores de Histona Desacetilase como estratégia terapêutica contra o câncer cervical humano associado ao Papilomavírus Humano (HPV)
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Data
2021-12-16
Autores
Behaker, Natália
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Universidade Estadual Paulista (Unesp)
Resumo
O câncer de colo de útero é o quarto tipo mais comum de câncer entre as mulheres. Sua principal causa é a infecção persistente pelo vírus Papilomavírus Humano (HPV) de alto risco, como o tipo 16 e o 18. As proteínas E6 e E7 do HPV são as responsáveis pela oncogênese, pois induz a replicação do genoma viral, proliferação não controlada, invasão, metástase, atividade da telomerase irrestrita, mecanismos de evasão de apoptose e influenciam a atividade de supressores de crescimento celular. Consequentemente, estas proteínas são o foco de pesquisas e terapias para o combate ao câncer cervical associado ao HPV. Os Inibidores de Histona Desacetilase (HDACIs) mostraram-se ser efetivos em estudos in vitro e in vivo, assim como adjuvantes promissores na terapia contra o câncer cervical associado ao HPV. Os HDACIs promovem a parada do ciclo celular, causando apoptose pela via intrínseca, reativam a expressão de genes supressores de tumor, anteriormente silenciados, e diminuem os níveis de proteínas do RNA mensageiro dos oncogenes E6 e E7, diminuindo a atividade do viral e a transformação celular. Poucos ensaios clínicos foram realizados usando HDACI para câncer cervical, mas alguns estudos envolvendo associação de fármacos parecem ser promissores. Como os medicamentos são caros e causam muitos efeitos colaterais, o tratamento em associação apresenta a possibilidade de resultados mais satisfatórios, considerando a diminuição dos efeitos colaterais devido à dose terapêutica inferior, diminuindo assim a toxicidade de ambos e promovendo uma qualidade de vida melhor a paciente. Os estudos de HDACIs no tratamento de câncer são bem promissores e tem bastante embasamento científico para acreditar que é uma boa estratégia para combater o câncer cervical associado ao HPV
Cervical cancer is the fourth most common type of cancer among women. It is mainly caused by the persistent infection with the high-risk Human Papillomavirus (HPV) viruses, such as type 16 and 18. HPV oncogenesis is related to E6 and E7 proteins responsible for many mechanisms, including viral genome replication, uncontrolled cell proliferation, invasion, metastasis, unrestricted telomerase activity, apoptosis evasion mechanisms, and influencing the activity of cell growth suppressors. Consequently, these proteins are the focus of research and therapies to combat cervical cancer associated with HPV. Histone Deacetylase Inhibitors (HDACIs) are effective in in vitro and in vivo studies, as well as promising adjuvants in therapy against HPV-associated cervical cancer. HDACIs promote cell cycle arrest, causing apoptosis through the intrinsic pathway, reactivate the expression of previously silenced tumor suppressor genes, and decrease the levels of messenger RNA proteins of the E6 and E7 oncogenes, decreasing viral activity and the cellular process. Although few clinical trials have been conducted using HDACIs for cervical cancer treatment, some drug-associated studies are promising. As drugs are expensive and cause many side effects, combination treatment presents the possibility of more satisfactory results, considering the reduction of side effects due to the lower therapeutic dose, thus reducing the toxicity of both and promoting a better quality of life for the patient. HDACIs studies in cancer treatment are very promising and provide evidence for treating HPV-associated cervical cancer
Cervical cancer is the fourth most common type of cancer among women. It is mainly caused by the persistent infection with the high-risk Human Papillomavirus (HPV) viruses, such as type 16 and 18. HPV oncogenesis is related to E6 and E7 proteins responsible for many mechanisms, including viral genome replication, uncontrolled cell proliferation, invasion, metastasis, unrestricted telomerase activity, apoptosis evasion mechanisms, and influencing the activity of cell growth suppressors. Consequently, these proteins are the focus of research and therapies to combat cervical cancer associated with HPV. Histone Deacetylase Inhibitors (HDACIs) are effective in in vitro and in vivo studies, as well as promising adjuvants in therapy against HPV-associated cervical cancer. HDACIs promote cell cycle arrest, causing apoptosis through the intrinsic pathway, reactivate the expression of previously silenced tumor suppressor genes, and decrease the levels of messenger RNA proteins of the E6 and E7 oncogenes, decreasing viral activity and the cellular process. Although few clinical trials have been conducted using HDACIs for cervical cancer treatment, some drug-associated studies are promising. As drugs are expensive and cause many side effects, combination treatment presents the possibility of more satisfactory results, considering the reduction of side effects due to the lower therapeutic dose, thus reducing the toxicity of both and promoting a better quality of life for the patient. HDACIs studies in cancer treatment are very promising and provide evidence for treating HPV-associated cervical cancer
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Palavras-chave
Cervical cancer associated with HPV, Câncer cervical associado ao HPV, Histonas Acetilase e Desacetilase, Inibidores de Histona Desacetilase e câncer, Inibidores de Histona Desacetilase e HPV, Histone Acetilase and Deacetylase, Histone Deacetylase and Cancer Inhibitors, Histone Deacetylase and HPV Inhibitors