New Anti Cancer Strategies Targeting Epigenetic Modifications And Associated Metabolism Reprogramming

The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders is now being translated into treatment approaches that target the epigenetic defects pharmacologically. This book first presents the latest evidence regarding the epigenetic regulation of hematopoietic stem cell differentiation and hemoglobin production. The significance of DNA methylation abnormalities in hematopoietic disorders and of epigenetic disturbances in lung cancer and other solid tumors is then discussed. A major part of the book, however, relates specifically to the translation of basic research and drug development to clinical applications, and in this context both present and future clinical strategies are considered. Individual chapters are devoted to the use of DNA hypomethylating agents and chromatin-modifying agents, and the treatment of hematologic malignancies and solid tumors by means of epigenetic agents is discussed in detail.

This book offers a broad overview of the concepts and research findings in immunometabolism. The immune system is made up of numerous different cell types, pathways, and components that must be able to respond rapidly to a pathogen or cancer, but must also remain quiescent in the absence of challenges. Immune cells rely on metabolic pathways to adapt to changing environments and stimuli. Additionally, these cells can be modified in function or fate by fluctuations in available nutrients. The chapters in this book describe ways in which immune cells utilize and are regulated by metabolic pathways. Topics include how immune-cell metabolism shapes immune homeostasis, and how dysregulation of these pathways can lead to immune disorders. In different contexts, such as a tumor microenvironment, immune-cell function and identity may be modified not only by cytokines and checkpoint molecules, but also by nutrient availability and other metabolic stimuli. Transcriptional reprogramming confers many of the changes in immune cell metabolism that are seen when a T-cell, for example, undergoes activation or functional adaptation to different environments. Lastly, immune cells can destructively or protectively participate in human metabolic homeostasis or disorders. This book summarizes immune-metabolism from a variety of different perspectives, including the ways in which metabolic cues, pathways, and requirements of immune cells change in conditions of homeostasis and activation. The exploration of the significance of metabolic checkpoints and other cues, particularly in the context of cancer and immune disorders, may form the foundation for the development of therapeutics.

The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.

This textbook presents concise chapters written by internationally respected experts on various important aspects of cancer-associated metabolism, offering a comprehensive overview of the central features of this exciting research field. The discovery that tumor cells display characteristic alterations of metabolic pathways has significantly changed our understanding of cancer: while the first description of tumor-specific changes in cellular energetics was published more than 90 years ago, the causal significance of this observation for the pathogenesis of cancer was only discovered in the post-genome era. The first 10 years of the twenty-first century were characterized by rapid advances in our grasp of the functional role of cancer-specific metabolism as well as the underlying molecular pathways. Various unanticipated interrelations between metabolic alterations and cancer-driving pathways were identified and currently await translation into diagnostic and therapeutic applications. Yet the speed, quantity, and complexity of these new discoveries make it difficult for researchers to keep up to date with the latest developments, an issue this book helps to remedy.

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.

NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.

Ergebnisse von in vitro-Studien lassen vermuten, dass sich der pH-Wert in einem Tumor auf die Wirksamkeit von Chemo- oder Strahlentherapien auswirken kann. Wie aber sieht die Beziehung zwischen der Tumorentwicklung und dem pH-Wert aus? Können ein niedriger pH-Wert oder ein Sauerstoffmangel die Carcinogenese hemmen? Wo bieten sich therapeutische Ansätze? Anwort auf diese und andere Fragen finden Sie in diesem Band. In interdisziplinärer Weise wurden Beiträge aus der Grundlagenforschung und der klinischen Praxis zusammengetragen.