Loading...
Publication
Estratégias de tratamento e prevenção das variantes genéticas BRCA1/BRCA2 no cancro da mama
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| 926.24 KB | Adobe PDF |
Authors
Advisor(s)
Abstract(s)
A síndrome do cancro da mama hereditário ou familiar apresenta uma das maiores taxas de mortalidade. As alterações germinativas nos genes do cancro da mama BRCA1 e BRCA2 associadas a esta síndrome foram diagnosticadas em cerca de 15% das mulheres afetadas.
Os BRCA1/2 são genes guardiões qual codificam proteínas supressoras de tumores que atuam no sistema de reparação por recombinação homóloga (HRR) mantendo a estabilidade genómica. Atuam sobretudo na reparação das quebras de cadeia dupla de ADN. Para além da HRR, também controlam a dinâmica dos
centrossomas, a segregação dos cromossomas, a citocinese e estabilizam o genoma no tempo e organização do ciclo celular. A instabilidade genómica devida à alteração no DNA conduzirá, portanto, a um ambiente cancerinogénico dependente de hormonas que contribuirá para o aparecimento de células malignas devido a uma HRR não funcional.
Para prevenir o aparecimento de cancro em mulheres com risco hereditário, é importante diagnosticar as mutações do gene BRCA. Se existir uma mutação, mas a mulher não tiver cancro, este pode ser prevenido através de um rastreio por ressonância magnética, mamografia, cirurgia de redução do risco e tratamentos hormonais preventivos.
Foi propósito deste estudo construir o estado de arte sobre a importância da deteção precoce dos genes BRCA1/2 e o seu tratamento, analisando diferentes estudos sobre a função destes genes, suas implicações no cancro da mama e sobre a eficácia de uma terapia com o alvo nestes genes. O desenvolvimento de tratamentos preventivos e direcionados para os genes BRCA1/BRCA2 aumenta a possibilidade de redução e
remissão do cancro da mama. O benefício adicional é o tratamento com terapia dirigida, ao contrário da quimioterapia, evitando a destruição de células saudáveis.
Hereditary or familial breast cancer syndrome has one of the highest mortality rates. Germline alterations in the BRCA1 and BRCA2 breast cancer genes associated with this syndrome have been diagnosed in around 15% of affected women. BRCA1/2 are guardian genes, tumor suppressor proteins that act in the homologous recombination repair (HRR) system to maintain genomic stability. They act mainly in the repair of DNA double-strand breaks. In addition to HRR, they also control centrosome dynamics, chromosome segregation, cytokinesis and stabilize the genome in time and spatially in the cell cycle. Genomic instability due to genomic deletion will therefore lead to a hormone-dependent carcinogenic environment that will contribute to the appearance of malignant cells due to a non-functional HRR. In order to prevent the onset of cancer in women with a hereditary risk of cancer, it is important to diagnose mutations in the BRCA gene. If there is a mutation, but the woman does not have cancer, it can be prevented through MRI screening, mammography, risk reduction surgery and preventive hormonal treatments. The aim of this study is to build the state of the art on the importance of early detection of the BRCA1/2 genes and their treatment, analyzing different studies on the function of these genes, their implications in breast cancer and the effectiveness of a therapy targeting these genes. The development of preventive and targeted treatments for the BRCA1/BRCA2 genes increases the possibility of breast cancer reduction and remission. The added benefit is that targeted therapy, unlike chemotherapy, avoids destroying healthy cells.
Hereditary or familial breast cancer syndrome has one of the highest mortality rates. Germline alterations in the BRCA1 and BRCA2 breast cancer genes associated with this syndrome have been diagnosed in around 15% of affected women. BRCA1/2 are guardian genes, tumor suppressor proteins that act in the homologous recombination repair (HRR) system to maintain genomic stability. They act mainly in the repair of DNA double-strand breaks. In addition to HRR, they also control centrosome dynamics, chromosome segregation, cytokinesis and stabilize the genome in time and spatially in the cell cycle. Genomic instability due to genomic deletion will therefore lead to a hormone-dependent carcinogenic environment that will contribute to the appearance of malignant cells due to a non-functional HRR. In order to prevent the onset of cancer in women with a hereditary risk of cancer, it is important to diagnose mutations in the BRCA gene. If there is a mutation, but the woman does not have cancer, it can be prevented through MRI screening, mammography, risk reduction surgery and preventive hormonal treatments. The aim of this study is to build the state of the art on the importance of early detection of the BRCA1/2 genes and their treatment, analyzing different studies on the function of these genes, their implications in breast cancer and the effectiveness of a therapy targeting these genes. The development of preventive and targeted treatments for the BRCA1/BRCA2 genes increases the possibility of breast cancer reduction and remission. The added benefit is that targeted therapy, unlike chemotherapy, avoids destroying healthy cells.
Description
Dissertação para obtenção do grau de Mestre no Instituto Universitário Egas Moniz
Keywords
Cancro da mama Mutações BRCA1/2 Tratamento Prevenção BRCA Cancro da mama hereditário