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Com os avanços na compreensão da forma como os mecanismos epigenéticos regulam
diversos processos celulares, tem-se percebido também que a epigenética, particularmente
a metilação do DNA, as modificações das histonas e o RNA não codificante, tem um papel
preponderante na formação e desenvolvimento de tumores. Como tal, focando no cancro
da próstata e no cancro da mama, este trabalho pretende compreender de que forma a
epigenética contribui para a formação de tumores malignos e como esse conhecimento tem
contribuído para avanços na abordagem à doença, fazendo, para isso, uma revisão da
literatura existente sobre o tema.
No cancro da próstata, a suspeita inicial é feita através do toque retal ou da medição dos
níveis de PSA, o que permite fazer um diagnóstico precoce, mas com o problema de uma
baixa especificidade. Visto que existem alterações epigenéticas desde o início da doença,
essas alterações têm sido usadas para o desenvolvimento de novas ferramentas de
diagnóstico que consigam prever com mais certeza o comportamento que o tumor terá,
havendo resultados promissores. Além disso, contribuiu também com a descoberta de
novos alvos terapêuticos, embora ainda haja um longo caminho.
No cancro da mama, também a nível do diagnóstico e da avaliação do prognóstico tem
havido avanços, com muitos métodos baseados em alterações epigenéticas a conseguirem
diferenciar entre os diferentes tipos e a conseguirem uma boa estratificação do risco. A nível
da terapêutica, embora a falta de especificidade e o excesso de toxicidade sejam um
problema, existem resultados promissores, nomeadamente no que toca a sinergias entre
drogas epigenéticas e quimioterapia convencional.
Apesar de todas as dificuldades que ainda existem, não há dúvida que o desenvolvimento
dos conhecimentos sobre o epigenoma farão parte do futuro da abordagem ao cancro.
With advances in the understanding of how epigenetic mechanisms regulate different cellular processes, it has become clear that epigenetics, particularly DNA methylation, histone modifications and non-coding RNA, play a major role in the formation and development of tumors. As such, focusing on prostate cancer and breast cancer, this work aims to understand how epigenetics contributes to the formation of malignant tumors and how this knowledge has contributed to advances in the approach to the disease, by reviewing existing literature on the topic. In prostate cancer, the initial suspicion is made by digital rectal examination or measurement of PSA levels, which allows for an early diagnosis, but with the problem of low specificity. Since there are epigenetic changes since the beginning of the disease, these changes have been used for the development of new diagnostic tools that are able to predict with more certainty the behavior that the tumor will have, with promising results. In addition, it has also contributed to the discovery of new therapeutic targets, although there is still a long way to go. In breast cancer, there have been advances in terms of diagnosis and assessment of prognosis as well, with many methods based on epigenetic changes being able to differentiate between different types and to achieve a good risk stratification. In terms of therapy, although lack of specificity and excess toxicity are a problem, there are promising results, particularly with regard to synergies between epigenetic drugs and conventional chemotherapy. Despite all the difficulties that still exist, there is no doubt that the development of knowledge about the epigenome will be part of the future of the approach to cancer.
With advances in the understanding of how epigenetic mechanisms regulate different cellular processes, it has become clear that epigenetics, particularly DNA methylation, histone modifications and non-coding RNA, play a major role in the formation and development of tumors. As such, focusing on prostate cancer and breast cancer, this work aims to understand how epigenetics contributes to the formation of malignant tumors and how this knowledge has contributed to advances in the approach to the disease, by reviewing existing literature on the topic. In prostate cancer, the initial suspicion is made by digital rectal examination or measurement of PSA levels, which allows for an early diagnosis, but with the problem of low specificity. Since there are epigenetic changes since the beginning of the disease, these changes have been used for the development of new diagnostic tools that are able to predict with more certainty the behavior that the tumor will have, with promising results. In addition, it has also contributed to the discovery of new therapeutic targets, although there is still a long way to go. In breast cancer, there have been advances in terms of diagnosis and assessment of prognosis as well, with many methods based on epigenetic changes being able to differentiate between different types and to achieve a good risk stratification. In terms of therapy, although lack of specificity and excess toxicity are a problem, there are promising results, particularly with regard to synergies between epigenetic drugs and conventional chemotherapy. Despite all the difficulties that still exist, there is no doubt that the development of knowledge about the epigenome will be part of the future of the approach to cancer.
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Palavras-chave
Cancro Epigenética Genes Mama Próstata