1,721,122 research outputs found
Histone deacetylase inhibitors: recent insights from basic to clinical knowledge & patenting of anti-cancer actions
No full textRole of the silencing of genes that encode for HDAC1 and HDAC2 in the cell line of acute myeloid leukaemia U937
No full textNatural compounds in epigenetics: A current view.
No full textThe successful treatment of many human diseases, including cancer, has come to be considered a major challenge, as patient response to therapy is difficult to predict. Recently, considerable efforts are being focused on the development of new tools to meet the growing demand for personalized medicine. With few exceptions, synthetic compounds have been unable to meet initial expectations for their clinical use. The last twenty years have been characterized by the failure of several drugs in advanced clinical development, possibly due to the insufficient understanding of molecular pathways underlying their mechanism of action. Although the biodiversity of compounds found in nature has been poorly explored until now, the field of naturally occurring drugs is rapidly expanding. Here, we review the current knowledge on the use of natural compounds with particular emphasis on those that display a chromatin remodeling effect coupled with anticancer action
Trials with 'epigenetic' drugs: An update.
Full text link""Epigenetic inactivation of pivotal genes involved in correct cell growth is a hallmark of human pathologies, in particular cancer. These epigenetic mechanisms, including crosstalk between DNA methylation, histone modifications and non-coding RNAs, affect gene expression and are associated with disease progression. In contrast to genetic mutations, epigenetic changes are potentially reversible. Re-expression of genes epigenetically inactivated can result in the suppression of disease state or sensitization to specific therapies. Small molecules that reverse epigenetic inactivation, so-called epi-drugs, are now undergoing clinical trials. Accordingly, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for cancer treatment have approved some of these drugs. Here, we focus on the biological features of epigenetic molecules, analyzing the mechanism(s) of action and their current use in clinical practice."
Histone deacetylase inhibitors: a patent review (2009 - 2011).
No full text"Introduction: Given the involvement of histone deacetylases (HDACs) in regulation of gene expression, they are believed to be 'master regulators' of many diseases. Thus, HDAC inhibitors (HDACis) are able to modulate transcriptional activity. These molecules can induce cell cycle arrest, differentiation and apoptosis of tumor cells in culture and in animal models and therefore are emerging as an exciting new class of potential anti-cancer agents for the treatment of solid and hematological malignancies. Areas covered: The aim of this review is to provide an overview of current knowledge and molecular mechanisms of HDACis, and the most recent patents existing in the field of HDACis from 2009 until 2011. Expert opinion: In recent years, an increasing number of structurally diverse HDACis have been identified. In addition, non-cancer diseases, including neurodegeneration, metabolic, inflammatory and autoimmune disorders, infectious and cardiovascular diseases have also been proposed for an HDACi treatment. The growing body of evidence of the potential benefits of disease treatment based on the use of HDACis has led to a large number of patent applications throughout the world
Genetic mutations in epigenetic modifiers as therapeutic targets in acute myeloid leukemia.
No full textDespite enormous insights into the molecular mechanisms of acute myeloid leukemia (AML) pathophysiology, this disease is still fatal in the majority of patients, highlighting the urgent need for novel biomarkers useful in AML prognosis and therapy. Areas covered: The advent of modern sequencing technologies has allowed the identification of genetic mutations in genes encoding for specific enzymes involved in the epigenetic regulation of gene expression. The authors review recent data demonstrating the involvement of mutations in genes encoding for epigenetic players and their complex combination with somatic genetic mutations in the pathogenesis of AML. They also discuss the prognostic and therapeutic implications of these findings. Expert opinion: Current clinical and preclinical studies are underscoring the importance of targeting epigenetic modifiers as new biomarkers for a better prognostic risk stratification and therapeutic evaluation of intermediate-risk patients. Combining data from traditional and modern methodologies will allow a definition of the complex networks of epigenetic changes and molecular interactions between candidate epitargets and key regulators of hematopoiesis. It will thus be possible to achieve an overview of potential aberrant mechanisms driving leukemogenesis in different classes of AML patients. Such an improved approach could pave the way towards 'personalized' therapies
- …
