Epigenetic Therapy of Cancer: Preclinical Models and Treatment Approaches

Epigenetic Therapy of Cancer: Preclinical Models and Treatment Approaches

by Michael Lubbert
     
 

The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders such as myeloid leukemias and preleukemias (myelodysplasias) is now being translated into treatment approaches that target the epigenetic defects pharmacologically. Such approaches include reactivation of tumor suppressor genes and other antiproliferative

See more details below

Overview

The growing knowledge about disturbances of epigenetic gene regulation in hematopoietic stem cell disorders such as myeloid leukemias and preleukemias (myelodysplasias) is now being translated into treatment approaches that target the epigenetic defects pharmacologically. Such approaches include reactivation of tumor suppressor genes and other antiproliferative genes by reversal of DNA hypermethylation through azanucleosides, and use of HDAC inhibitors to reverse gene silencing mediated by chimeric, leukemia-specific transcription factors.

This book first presents the latest evidence derived from preclinical models 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.

Read More

Editorial Reviews

Doody's Review Service
Reviewer: Gerd Pfeifer, PhD (City of Hope)
Description: Today, it is widely recognized that cancer is not only a genetic disease but that alterations of the epigenome (the heritable regulatory information that is superimposed on the genome) are perhaps equally important for tumor formation. This understanding comes from numerous studies that have identified epigenetic changes in cancer cells, both in the form of aberrations in DNA methylation and in histone modification patterns. Moreover, genes coding for epigenetic modifiers that function to alter DNA and histone modifications, such as DNA methyltransferases, 5-methylcytosine oxidases, histone lysine methyltransferases and demethylases, are all frequently mutated in a diverse set of human cancers. This new book covers the timely topic of epigenetic therapy.
Purpose: The objective of the authors was to systematically review recent developments ranging from basic research in epigenetics of cancer to drug development and clinical applications of epigenetic therapy in hematology and oncology. The book serves an unmet need to summarize this emerging field of clinical research and the authors have done an excellent job of accomplishing their objectives.
Audience: The combination of articles describing the basic science framework of epigenetics and the detailed summaries of clinical trials with epigenetic drugs is attractive for a wide readership, ranging from medical students to scientists who are interested in translational studies to clinicians who work for the direct benefit of cancer patients. The authors are leaders in this area and they have assembled a highly qualified team of experts for each of the 13 chapters.
Features: The book begins with several reviews summarizing the basic science of epigenetics with a focus on describing the functional components of these processes in general terms, as well as alterations that are found in cancer tissue and several mouse models of DNA methylation deficiency. Since much of the book focuses on hematological malignancies, epigenetic regulation in normal hematopoiesis as well as in pathological conditions is described. One chapter is a comprehensive overview of epigenetic aberrations induced by MLL fusion proteins in leukemia. An additional chapter dealing with mutations in epigenetic modifier genes would have been helpful. These discoveries are very recent and will certainly contribute to our knowledge of aberrant epigenetic states in different malignancies. The next set of chapters shifts towards treatment of hematological malignancies with epigenetic drugs, with an emphasis on the classical epigenetic drug 5-azacytidine and its deoxynucleoside derivative, 5-azadeoxycytidine. These DNA methylation inhibitors have been extensively and successfully tested in clinical trials for treatment of MDS and AML and are FDA-approved. These comprehensive and detailed reviews are complemented by other chapters that discuss the clinical use of histone deacetylase (HDAC) inhibitors. These therapeutic agents have shown promise for various malignancies and are often used alone or in combination therapies. One chapter describes the basic biology of histone lysine and arginine methyltransferases and the development of specific inhibitors for these enzymes. It can be expected that a number of such drugs as well as inhibitors of histone demethylases will find their way into clinical trials. To maximize efficiency of these treatments, mapping of the actual aberrant chromatin state before and after drug treatment in tumors may become a component of individual patient management. The book ends with a group of chapters that discuss the problems and challenges of applying epigenetic drugs to solid tumors, which so far has met with somewhat limited success. Some initial promising results give hope, however, that this group of malignancies can eventually be targeted more effectively with epigenetic therapeutic drugs in the future.
Assessment: This high-quality book is an excellent overview of the current success and future promise of epigenetic therapy. Its unique combination of topics covering basic research findings and clinical applications reflects the state of the field in which discoveries from the laboratory have effectively been translated into treatment options for cancer patients.

Read More

Product Details

ISBN-13:
9783642384035
Publisher:
Springer Berlin Heidelberg
Publication date:
01/31/2014
Edition description:
2014
Pages:
325
Product dimensions:
6.20(w) x 9.20(h) x 0.90(d)

Customer Reviews

Average Review:

Write a Review

and post it to your social network

     

Most Helpful Customer Reviews

See all customer reviews >