RESUMO
O grande desenvolvimento da pesquisa em genômica nas últimas décadas tem gerado muitas expectativas com relação ao seu impacto na biomedicina. Observa-se o crescente investimento em pesquisa na medicina personalizada ou de precisão, que busca customizar a prática médica com foco no indivíduo baseando-se na utilização de testes genéticos, identificação de biomarcadores e desenvolvimento de medicações alvo. O movimento da medicina personalizada ou de precisão, no entanto, é polêmico e tem suscitado um importante debate entre seus defensores e críticos. Este ensaio teve por objetivo discutir os pressupostos, promessas, limites e possibilidades da medicina personalizada ou de precisão com base em uma revisão da literatura recente situando o debate sobre o tema. A revisão aponta que muitas das promessas da medicina personalizada ou de precisão ainda não se concretizaram. Se por um lado houve enorme avanço no conhecimento sobre os mecanismos moleculares das patologias e o desenvolvimento de medicamentos que impactaram significativamente o tratamento de alguns tipos de câncer, até o momento não há evidências de que este padrão se reproduzirá em outras doenças complexas. A medicina personalizada ou de precisão deve gerar desenvolvimentos incrementais em áreas específicas da medicina, existindo, no entanto, vários obstáculos para sua generalização. O alto custo das novas biotecnologias pode agravar as desigualdades em saúde, tornando-se um problema para a sustentabilidade dos serviços de saúde, especialmente em países de média e baixa rendas. A ênfase na medicina personalizada ou de precisão pode levar ao deslocamento de recursos financeiros de iniciativas menos custosas e com maior impacto em saúde pública.
El gran desarrollo de la investigación en genómica en las últimas décadas ha generado muchas expectativas en relación con su impacto en la biomedicina. Se observa la creciente inversión en investigación en medicina personalizada o de precisión, que busca hacer a medida la práctica médica, centrándose en el individuo, basándose en la utilización de pruebas genéticas, identificación de biomarcadores y desarrollo de medicamentos diana. El movimiento de la medicina personalizada o de precisión, no obstante, es polémico y ha suscitado un importante debate entre sus defensores y críticos. Este ensayo tuvo como objetivo discutir los presupuestos, promesas, límites y posibilidades de la medicina personalizada o de precisión, en base a una revisión de la literatura reciente, situando el debate sobre este tema. La revisión apunta que muchas de las promesas de la medicina personalizada o de precisión todavía no se concretizaron. Si por un lado hubo un enorme avance en el conocimiento sobre los mecanismos moleculares de las patologías, y el desarrollo de medicamentos que impactaron significativamente el tratamiento de algunos tipos de cáncer, hasta el momento no hay evidencias de que este patrón se reproducirá en otras enfermedades complejas. La medicina personalizada o de precisión debe generar desarrollos incrementales en áreas específicas de la medicina, existiendo, no obstante, varios obstáculos para su generalización. El alto coste de las nuevas biotecnologías puede agravar las desigualdades en salud, convirtiéndose en un problema para la sostenibilidad de los servicios de salud, especialmente en países de media y baja renta. El énfasis en la medicina personalizada o de precisión puede llevar al desplazamiento de recursos financieros de iniciativas menos costosas y con mayor impacto en salud pública a otras de esta índole.
The enormous development of genomics research in recent decades has raised great expectations concerning its impact on biomedicine. There has been growing investment in research in personalized or precision medicine, which aims to customize medical practice with a focus on the individual, based on the use of genetic tests, identification of biomarkers, and development of targeted drugs. However, the personalized or precision medicine movement is controversial and has sparked an important debate between its defenders and critics. This essay aims to discuss the assumptions, promises, limits, and possibilities of personalized or precision medicine based on a review of the recent literature situating the debate on the theme. The review indicates that many of the promises of personalized or precision medicine remain unfulfilled. While there has been huge progress in knowledge on the molecular mechanisms of diseases and the development of drugs that have significantly impacted the treatment of some types of cancer, thus far there is no evidence that this same pattern will be reproduced in other complex diseases. Personalized or precision medicine is expected to generate incremental developments in specific areas of medicine, but there are obstacles to its generalization. The high cost of new biotechnologies can exacerbate health inequalities and become a problem for health services' sustainability, especially in low and middle-income countries. The emphasis on personalized or precision medicine may shift funds away from less costly interventions that have greater public health impact.
Assuntos
Humanos , Tecnologia Biomédica/tendências , Medicina de Precisão/tendências , Preparações Farmacêuticas/economia , Equidade em Saúde , Tecnologia Biomédica/economia , Genômica/economia , Genômica/métodos , Medicina de Precisão/economia , Neoplasias/economia , Neoplasias/terapiaRESUMO
OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Genômica/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Análise de Sequência de DNA/métodos , Progressão da Doença , Intervalo Livre de Doença , Genômica/tendências , Estimativa de Kaplan-Meier , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Neoplasias/mortalidade , Neoplasias/patologia , Medicina de Precisão/métodos , Receptor ErbB-2/antagonistas & inibidores , Reprodutibilidade dos Testes , Análise de Sequência de DNA/tendências , Fatores de Tempo , Resultado do TratamentoRESUMO
El parto pre-término es el mayor reto de la medicina perinatal. Nos propusimos analizarlo para conocer su repercusión en la morbimortalidad perinatal y la morbilidad materna, y finalmente conocer los alcances de la medicina genómica sobre esta entidad perinatal. Se realiza una revisión sistemática y análisis de las publicaciones que sobre esta patología se han originado en este hospital desde 1970 a abril 2010 siguiendo una linea de investigación propia de 32 años. Ademas se revisó la literatura mundial en las bases de datos médicos en internet desde 1982 a la actualidad para obtener la relación científica de la medicina genómica y el parto pre-término. La incidencia del parto pre-término estudiada en dos series con 636 casos en el lapso 2003-2007 revelo promedio porcentual de 4.19. La incidencia de morbi-mortalidad perinatal analizada en cuatro series de parto pre-terminó que totalizan 1.441 casos 1991-2007, la morbilidad promedio fue 27,79%, la mortalidad perinatal 38,18%, lamortalidad fetal 21,66% y la mortalidad neonatal 15,62%, la patología primaria fue el síndrome de insuficiencia respiratoria. La participación del parto pre-término en la mortalidad perinatal (muerte fetal y neonatal) encontrada en cuatro publicaciones con total de 1430 muertes 1993-2002 fue de 68,65%. El aporte del parto pre-término en la morbilidad materna evaluada por hospitalización antenatal, en muestra de 256 gestantes años 1991-1993, se asoció al 23,4 como amenaza de parto pre-termino % y en una población de 1326 gestantes hospitalizadas aportó 25,72%. La medicina genómica se muestra como una alternativa novedosa ante el parto pre-término, con tecnólogía de avanzada, en los conocimientos etiogénicos, recursos diagnósticos y terapéuticos precoces y posibles acciones preventivas futurísticas. Se concluye que el parto pre-término implica elevadas cifras de morbimortalidad perinatal, aportada principalmente por deficiencias respiratorias, además incide en la morbilidad materna...
The pre-term birth is the greatest challenge in perinatal medicine. We set analyzes their repercussion to perinatal morbidity and maternal morbidity, and finally to know the scope of genomic medicine perinatal about this entity. We performed a systematic review and analysis of published literature on this entity that have sprung up in this hospital from 1970 to April 2010 following a line of own research of 32 years. Also reviewed the world literature in medical databases on the Internet from 1982 to present for the scientific relationship of genomic medicine and pre-term birth. The incidence of pre-term birth studied in two series with 636 cases in the period 2003-2007 showed an average percentage rate of 4.19. The incidence of perinatal morbidity and mortality analyzed in four series totaling 1441 cases of pre-term birth, period 1991-2007, the average morbidity was 27.79%, perinatal mortality 38.18%, fetal mortality 21.66% and neonatal mortality 15,62%, the primary pathology was respiratory distress syndrome. The morbidity and perinatal mortality (fetal and neonatal death) was studied in four publications with total of 1439 dealths, 1993-2002, 68,65% were the pre-term births. The impact of pre-term birth in morbidity assessed by antenatal hopitazation in a sample of 256 pregnant years 1991-1993, was associated with 23.4% and a population of 1326 pregnant women hospitalized contributed 25.72% with pre-term labor. Genomic medicine is shown as a novel alternative to pre-term birth with advanced technology, in knowledge etiology, early diagnostic and therapeutic resources and possible preventive actions futuristic. We conclude that pre-term birth involves high perinatal morbidity and mortality figures, contributed mainly by respiratory distress also affects maternal morbidity. Genomic medicine is looming, with promising hopes etiopathogenic and behavior. Meanwhile, we must emphasize prevention programs and improved neonatal care