Bernhard Haendler – författare

Methylation of DNA at cytosine residues as well as post-translational modifications of histones, including phosphorylation, acetylation, methylation and ubiquitylation, contribute to the epigenetic information carried by chromatin. These changes play an important role in the regulation of gene expression by modulating the access of regulatory factors to the DNA. The use of a combination of biochemical, genetic and structural approaches has allowed demonstration of the role of chromatin structure in transcriptional control. The structure of nucleosomes has been elucidated and enzymes involved in DNA or histone modifications have been extensively characterized. Since deregulation of epigenetic marks has been reported in many cancers, a better understanding of the underlying molecular mechanisms bears the promise that new drug targets may soon be found. The newest developments in this quickly developing field are presented in this book.

Cancer stem cells werehave originally been identified in leukemia and later in several solid tumor types. They have very different properties from the bulk of the tumor, as they divide much more slowly and have very efficient drug- resistance mechanisms. Current treatments might largely spare cancer stem cells, thus leading to tumor recurrence and metastasis. The recent identification of growth and differentiation pathways responsible for cancer stem cell proliferation and survival will help in the discovery identification of novel therapeutic targets. Developing selective drugs against cancer stem cells offers great therapeutic opportunities but also provides for major challenges regarding preclinical models, therapeutic windows, and clinical study end points.