Epigenetic Therapy of Cancer Preclinical Models and Treatment Approaches

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.

The fundamental role of epigenetic regulation for normal and disturbed all growth and differentiation.- Mouse models to study DNA methylation in cancer research.- Epigenetic regulation of normal hematopoietic development.- Epigenetic regulation of globin genes and disturbances in hemoglobinopathies.- DNA methylation abnormalities in hematopoietic disorders: biological significance and methodological approaches.- Epigenetic modifications mediated by the AML1/ETO and MLL leukemia fusion proteins.- Epigenetic abnormalities in lung cancer.- Pharmacodynamic Responses to DNA Methyltransferase Inhibition.- Histone Methyltransferases: Opportunities in Cancer Drug Discovery.- Histone deacetylase (HDAC) inhibitors in recent clinical trials for cancer therapy.- Clinical Implications of Epigenetic Alterations in Lung Cancer.- Epigenetic disturbances in colorectal cancer.- Epigenetic Therapies in Solid Tumours: from preclinical models to clinical trial results.