Publication: Desarrollo de estrategias basadas en técnicas moleculares y test farmacológicos para la implantación de protocolos de medicina personalizada en el tratamiento del mieloma múltiple
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2019-08-02
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Universidad Complutense de Madrid
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Abstract
El Mieloma Múltiple (MM) es la segunda neoplasia hematológica más frecuente y se caracteriza por la proliferación descontrolada de células plasmáticas en la médula ósea. El reciente desarrollo de nuevas terapias ha permitido aumentar las opciones terapéuticas y mejorar considerablemente las expectativas de vida de estos pacientes, aunque todavía es incurable. La marcada variabilidad en la respuesta a los tratamientos y en la supervivencia los pacientes ponen de manifiesto la necesidad de identificar nuevos factores pronóstico y predictores de respuesta al tratamiento que permitan encontrar la mejor aproximación terapéutica para cada individuo, de manera personalizada. En este contexto, la reciente aparición de técnicas de secuenciación masiva del ADN como la secuenciación de nueva generación ha permitido conocer muy en profundidad las enormes variabilidades genéticas que presentan las células tumorales de mieloma, tanto entre pacientes como dentro de un mismo paciente. Sin embargo, mayores esfuerzos deber realizarse para poder encontrar nuevas dianas terapéuticas y biomarcadores de respuesta al tratamiento, ya que actualmente la elección de este se basa en la pericia clínica del médico y no en base al perfil mutacional del tumor..
Multiple myeloma (MM) is a hematological neoplasia that develops after transformation and excessive growth of plasma cells at the bone marrow. MM is characterized by a heterogeneous genetic abnormality and an extensive range of clinical outcomes. The development of more sophisticated therapeutic drugs such as immunomodulatory agent or proteasome inhibitors have expanded the clinical options for MM patients. However, the marked variability of responses to these treatments highlights the need to identify new biomarkers of response. Currently, most hospitals use conventional karyotyping and fluorescence in situ hybridization (FISH) to identified cytogenetic abnormalities. Nevertheless, the genetic aberrations detected by these methods have a limited prognostic value, justifying the incorporation of a more comprehensive method for the genetic screening into the diagnostic workup. The recent introduction of next-generation sequencing (NGS) technologies has considerably advanced our understanding of the biological features of MM. Targeted sequencing studies facilitate the detection of mutations in known genes, including those at low allele frequencies. Thus, it is an excellent tool to complement conventional molecular and cytogenetic approaches in the clinic routine. Targeted sequencing has been used to identify prognostic markers and achieve better patient stratification over the las few years. Despite of great efforts, it has not been found a clear relation between the presence of subclones and the sensitivity to treatments.Additionally...
Multiple myeloma (MM) is a hematological neoplasia that develops after transformation and excessive growth of plasma cells at the bone marrow. MM is characterized by a heterogeneous genetic abnormality and an extensive range of clinical outcomes. The development of more sophisticated therapeutic drugs such as immunomodulatory agent or proteasome inhibitors have expanded the clinical options for MM patients. However, the marked variability of responses to these treatments highlights the need to identify new biomarkers of response. Currently, most hospitals use conventional karyotyping and fluorescence in situ hybridization (FISH) to identified cytogenetic abnormalities. Nevertheless, the genetic aberrations detected by these methods have a limited prognostic value, justifying the incorporation of a more comprehensive method for the genetic screening into the diagnostic workup. The recent introduction of next-generation sequencing (NGS) technologies has considerably advanced our understanding of the biological features of MM. Targeted sequencing studies facilitate the detection of mutations in known genes, including those at low allele frequencies. Thus, it is an excellent tool to complement conventional molecular and cytogenetic approaches in the clinic routine. Targeted sequencing has been used to identify prognostic markers and achieve better patient stratification over the las few years. Despite of great efforts, it has not been found a clear relation between the presence of subclones and the sensitivity to treatments.Additionally...
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Tesis de la Universidad Complutense de Madrid, Facultad de Medicina, Departamento de Medicina Interna, leída el 10-05-2019