Epigenetic management of cancer: promise versus practice.
Speaker: María Berdasco Menéndez
Instituto de Investigación Biomédica de Bellvitge (IDIBELL) [Barcelona]
Host: Eugenio Santos / Xosé R. Bustelo
Salón de actos del Centro de Investigación del Cáncer
Among the diverse molecular pathways that govern cancer, epigenetics can guide tumor development and progression in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Genome-wide epigenome analysis of human health and disease (mainly cancer but not limited to) are now available and form part of a complex network with genetic and environmental data. As a consequence of this integrative vision, we can found a plethora of preclinical studies providing a large list of candidates based on differential DNA methylation, altered histone modifications as well as changes in ncRNA expression (especially miRNA) that have a relevant role in tumorogenesis.
Rather than providing a broad description of the pathways epigenetically deregulated in human malignancies, the seminar will be focused on the current and future use of epigenetics for a better management of cancer, including its use as biomarkers of risk, prognostic factors and therapy-predictors (“pharmacoepigenetics”). As example, the existence of specific profiles of genomic sequences that undergo a shared gain or loss of CpG methylation has been used to subclasify tumors in molecular subtypes or to identify the primary tumor in metastatic patients with carcinoma of unknown origin. In addition to their use as biomarkers, the reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets for “epidrugs” (e.g., histone desacetylase inhibitors to treat hematological malignancies).
In spite of clinical epigenetics emerging as an appealing alternative approach to the management of cancer with deregulation in multiple signalling pathways, many unresolved questions still hinder the progression of candidate biomarkers or therapies to clinical trials. The seminar will shed light into the challenges that need to be overcome to implement clinical epigenetics. Specifically, we point out some gaps in epigenetic knowledge (e.g., methodological limitations, epigenetic causality or the emerging field of epitranscriptomics) that should be addressed over the coming years.