Histone Deacetylase Inhibitors As Cancer Therapeutics

Provides information on the exciting and fast-moving field of cancer research.

This book reviews the latest developments in the design, synthesis, and molecular mechanism of action of Histone Deacetylase (HDAC) inhibitors in the context of potential cancer therapy. HDAC inhibitors are emerging as promising anticancer drug molecules that promote growth arrest, differentiation and apoptosis of cancer cells with tumor selective toxicity. The book begins with an overview of various epigenetic modifying enzymes that are involved in cancer transition and progression; before exploring the potential of HDACs in cancer treatment. It provides a classification of HDAC inhibitors based on their structural attributes, and addresses HDAC-induced cytotoxicity.. Lastly, it discusses and assesses the rationale behind therapies that combine HDAC inhibitors with other anticancer agents to treat solid tumors. Given its scope, it offers a valuable resource for all researchers, clinicians, and students working in formulation, drug discovery, oncology, and personalized medicine.

There have been tremendous advances in our understanding of molecular and tumor biology during the past few years. In the field of cancer therapeutics, it is expected that cytotoxic drug approaches will be gradually replaced with treatments based on biological targeted approaches. Hopefully these new targeted therapies will significantly increase efficacy and lack the devastating and troublesome side effects elicited by cytotoxic chemotherapy. This volume is the first book to cover the general topic of targeted cancer therapy. It presents a range of targets such as tumor angiogenesis, cell cycle control and cell signalling, COX-2, apoptosis/cell survival, invasion and metastasis and approaches like kinase inhibitors, antisense, and antibody-based therapeutics. The emphasis is on preclinical development, including target validation, development of biomarkers, strategies for combination approaches, and development of resistance. The particular challenges involved in translating these data to clinical application are discussed. This volume should be of broad general interest to researchers and clinicians involved in cancer therapy as well as other scientists interested in current strategies for cancer treatment.

Histone deacetylase 1 / Dominique Meunier and Christian Seiser -- Biochemistry of multiprotein HDAC complexes / Alejandro Vaquero, Michael Scher, and Danny Reinberg -- The biology of HDAC3 / Edward Seto -- The biology of HDAC8, a unique class I histone deacetylase / David Waltregny and Vincent Castronovo -- Regulation of muscle gene expression by histone deacetylases / Timothy A. McKinsey and Eric N. Olson -- The class IIA histone deacetylases: functions and regulation / Herbert G. Kasler and Eric Verdin -- Histone deacetylases in the response to misfolded proteins / J. Andrew McKee and Tso-Pang Yao -- Evolution of sirtuins from archaea to vertebrates / Roy A. Frye -- Structure of the Sir2 family of NAD+-dependent histone/protein deacetylases / Kehao Zhao and Ronen Marmorstein -- The enzymology of Sir2 proteins / Margie T. Borra and John M. Denu -- The class III protein deacetylases: homologs of yeast Sir2P / Bjoern Schwer ... [et al.] -- HDAC inhibitors: discovery, development, and clinical impacts / Akihiro Ito, Norikazu Nishino, and Mitsuaki Yoshida -- Cell cycle targets of histone deacetylase inhibitors / Brian Gabrielli -- HDAC inhibitors: an emerging anticancer therapeutic strategy / Paul Kwon, Meier Hsu, Dalia Cohen, and Peter Atadja.

This volume will cover the natural products as they relate to cancer chemotherapy. The topics will include history and current status , recent launches, new clinical candidates and approved drugs directly derived from natural products, current and future cancer target opportunities for natural products, leveraging natural products as tools for new target generation , new approaches to cancer drug discovery through natural products based lead generation, and enabling technologies which leverage the unique attributes of natural products.