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Análise genética do perfil tumoral como fator adicional na abordagem ao doente oncológico : estudo de caso
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Resumo(s)
As doenças oncológicas são muito prevalentes e o cancro da mama é a neoplasia mais frequente e de maior mortalidade na mulher. A compreensão dos processos moleculares e das alterações genéticas subjacentes às neoplasias, permite o desenvolvimento de terapêuticas específicas, que podem alterar a abordagem terapêutica dos doentes. O Comprehensive Genetic Profiling realizado através da sequenciação genética de nova geração utilizada pela FoundationOne® CDx é uma das formas de termos acesso a alterações genéticas tumorais clinicamente significativas. Estas alterações genéticas e moleculares podem evoluir ao longo da progressão da doença e por vezes serem responsáveis pelo surgimento de mecanismos de resistência à terapêutica. O estudo do caso apresentado ilustra a heterogeneidade e a capacidade evolutiva das células tumorais e permite-nos analisar de que forma o conhecimento das mutações presentes nas células tumorais pode modificar a nossa abordagem terapêutica. Neste caso, a evolução da doença fez-nos perceber que, apesar dos marcadores avaliados por imunohistoquímica ou hibridização in situ nos direcionarem para uma terapêutica preferencial, existem outras alterações (detetadas com a análise genética) que predizem diferentes respostas a uma mesma terapêutica. Assim sendo, no caso apresentado, a análise genética permitiu perceber a razão pela qual o tumor se mantinha resistente e com capacidade de provocar progressão da doença, apesar da terapêutica dirigida ao human epidermal growth factor receptor 2 (HER-2). No caso apresentado detetou-se uma mutação onde seria possível atuar e esta descoberta alterou a abordagem terapêutica deste caso em particular. No entanto, não foi possível concluir se esta alteração na terapêutica se refletiu numa alteração do curso da doença e numa melhoria dos outcomes.
Oncologic diseases are very prevalent and breast cancer is, among women, one of the most frequent cancers and with most mortality. The understanding of molecular processes and genetic changes related to cancer allows the development of specific therapeutics, which can change the therapeutic approach to patients. One way to have access to clinically significant tumoral genetic changes is by performing a Comprehensive Genetic Profiling carried through Next Generation Sequencing (a method used by FoundationOne® CDx). These genetic and molecular changes can evolve with the disease progress and are sometimes responsible for the emergence of mechanisms resistant to therapy. The study case shows the heterogeneity and the evolutionary capacity of tumoral cells and allows us to analyse in which way the knowledge of mutations within tumoral cells may affect our therapeutic approach. In this case, the disease evolution made us understand that, despite the markers evaluated by immunohistochemistry or in situ hybridization lead us to a preferential therapy, there are other alterations (detected with genetic analysis) which predict different reactions to the same therapy. Therefore, in the presented case, the genetic analysis enabled us to comprehend the reason why the tumour remains resistant and capable of inducing the disease progression, despite of the human epidermal growth factor receptor 2 (HER-2) directed therapy. In this case, it was possible to detect a mutation where we could potentially act and this discovery changed the therapeutic approach of this case in particular. However, it was not possible to conclude if this therapeutic change was reflected in a modification of the disease course and an improvement of the outcomes.
Oncologic diseases are very prevalent and breast cancer is, among women, one of the most frequent cancers and with most mortality. The understanding of molecular processes and genetic changes related to cancer allows the development of specific therapeutics, which can change the therapeutic approach to patients. One way to have access to clinically significant tumoral genetic changes is by performing a Comprehensive Genetic Profiling carried through Next Generation Sequencing (a method used by FoundationOne® CDx). These genetic and molecular changes can evolve with the disease progress and are sometimes responsible for the emergence of mechanisms resistant to therapy. The study case shows the heterogeneity and the evolutionary capacity of tumoral cells and allows us to analyse in which way the knowledge of mutations within tumoral cells may affect our therapeutic approach. In this case, the disease evolution made us understand that, despite the markers evaluated by immunohistochemistry or in situ hybridization lead us to a preferential therapy, there are other alterations (detected with genetic analysis) which predict different reactions to the same therapy. Therefore, in the presented case, the genetic analysis enabled us to comprehend the reason why the tumour remains resistant and capable of inducing the disease progression, despite of the human epidermal growth factor receptor 2 (HER-2) directed therapy. In this case, it was possible to detect a mutation where we could potentially act and this discovery changed the therapeutic approach of this case in particular. However, it was not possible to conclude if this therapeutic change was reflected in a modification of the disease course and an improvement of the outcomes.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2019
Palavras-chave
Cancro da mama Sequenciação genética de nova geração Comprehensive genetic profiling Foundation Medicine® Oncologia