Epigenetics In Cancer Mechanisms And Drug Development

This book will provide an invaluable guide to epigenetics, one of the fastest moving fields in drug discovery, for medicinal chemists working in academia and in the pharmaceutical industry.

Epigenetic Mechanisms in Cancer provides a comprehensive analysis of epigenetic signatures that govern disease development, progression and metastasis. Epigenetic signatures dictating tumor etiologies present an opportunity for biomarker identification which has broad potential for improving diagnosis, prognosis, prediction, and risk assessment. This volumes offers a unique evaluation of signature differences in childhood, sex-specific and race-specific cancers, and in doing so broadly illuminates the scope of epigenetic biomarkers in clinical environments. Chapters detail the major epigenetic process in humans consisting of DNA methylation, histone modifications and microRNAs (miRNAs) involved in the initiation, progression and metastasis of tumors. Also delineated are recent technologies such as next generation sequencing that are used to identify epigenetic profiles (primarily methylation analysis) in samples (normal, benign and cancerous) and which are highly important to the analysis of epigenetic outcomes.

Drug Discovery in Cancer Epigenetics is a practical resource for scientists involved in the discovery, testing, and development of epigenetic cancer drugs. Epigenetic modifications can have significant implications for translational science as biomarkers for diagnosis, prognosis or therapy prediction. Most importantly, epigenetic modifications are reversible and epigenetic players are found mutated in different cancers; therefore, they provide attractive therapeutic targets. There has been great interest in developing and testing epigenetic drugs, which inhibit DNA methyltransferases, histone modifying enzymes or chromatin reader proteins. The first few drugs are already FDA approved and have made their way into clinical settings. This book provides a comprehensive summary of the epigenetic drugs currently available and aims to increase awareness in this area to foster more rapid translation of epigenetic drugs into the clinic. Highlights the potential of epigenetic alterations in cancer for drug development Covers the tools and methods for epigenetic drug discovery, preclinical and clinical testing, and clinical implications of epigenetic therapy Provides important information regarding putative epigenetic targets, epigenetic technologies, networks and consortia for epigenetic drug discovery and routes for translation

Many inheritable changes in gene function are not explained by changes in the DNA sequence. Such epigenetic mechanisms are known to influence gene function in most complex organisms and include effects such as transposon function, chromosome imprinting, yeast mating type switching and telomeric silencing. In recent years, epigenetic effects have become a major focus of research activity. This monograph, edited by three well-known biologists from different specialties, is the first to review and synthesize what is known about these effects across all species, particularly from a molecular perspective, and will be of interest to everyone in the fields of molecular biology and genetics.

Establishment of a normal phenotype involves dynamic epigenetic regulation of gene expression that when affected contributes to human diseases. On a molecular level, epigenetic regulation is marked by specific covalent modifications (acetylation, methylation, phosphorylation, sumoylation, PARylation and ubiquitylation) of DNA and its associated histones. Studies also suggest the influence of such epigenetic modifications on non-coding RNA expression implicated in normal and diseased phenotypes. Epigenetic control of genetic expression is a reversible process essential for normal development and function of an organism. Alteration of epigenetic regulation leads to various disease forms such as cancer, diabetes, inflammation and neuropsychiatric disorders. Assessing these alterations provides a deeper insight into the changes induced in the genome, which is often informative for identifying disease subtypes or developing suitable treatments. Therefore, epigenetics proves to be a key area of clinical investigation in diagnosis, prognosis, and treatment of complex diseases. Genetic mutations, environmental stress, pathogens and drugs of abuse are some of the predominant factors that induce and impact changes on chromatin, which directly dictate a diseased phenotype. It is essential to consider the interaction between genetic and epigenetic factors to understand the molecular mechanisms of complex human diseases for safer and efficient drug development. Furthermore, genetic variation in absorption, distribution, metabolism, and excretion (ADME) genes is insufficient to account for interindividual variability of drug response. Therefore, current efforts aim to identify epigenetic components of ADME gene regulation, which include phase-I and phase-II enzymes, uptake transporters, efflux transporters and nuclear receptors involved in regulation of ADME genes. Monitoring circulatory epigenetic biomarkers in liquid biopsies (blood, saliva, urine, cerebrospinal fluid) of disease-associated and drug-associated epigenetic alterations may prove useful for decision support for routine clinical treatment and drug discovery. Hence, recent drug discovery efforts on targeting the epigenome, has emerged an area of interest with several new drugs being developed, tested and some already approved by the US Food and Drug Administration (FDA). These new insights into the complexities of epigenetic regulation are key contributors to our basic understanding of this process in human health and disease, which will provide scope for innovative drug therapies. It is of urgency to aid the present understanding of epigenomics driven diseased outcomes, with the expectation that further studies will identify early markers of disease and targets for therapeutics.

Epigenetic Mechanisms in Cancer provides a comprehensive analysis of epigenetic signatures that govern disease development, progression and metastasis. Epigenetic signatures dictating tumor etiologies present an opportunity for biomarker identification which has broad potential for improving diagnosis, prognosis, prediction, and risk assessment. This volumes offers a unique evaluation of signature differences in childhood, sex-specific and race-specific cancers, and in doing so broadly illuminates the scope of epigenetic biomarkers in clinical environments. Chapters detail the major epigenetic process in humans consisting of DNA methylation, histone modifications and microRNAs (miRNAs) involved in the initiation, progression and metastasis of tumors. Also delineated are recent technologies such as next generation sequencing that are used to identify epigenetic profiles (primarily methylation analysis) in samples (normal, benign and cancerous) and which are highly important to the analysis of epigenetic outcomes. Offers broad coverage that is applicable to audiences in various area of cancer research - population studies, diagnostics, prognosis, prediction, therapy, risk, etc. Provides critical review analysis of the topics that will clarify and delineate the potential roles of epigenetic signatures in cancer management Covers basic, as well as, clinical areas of epigenetic mechanisms in tumorigenesis Features contributions by leading experts in the field Provides comprehensive coverage of current epigenetic signatures involved in the etiology of various cancers and miRNAs