Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor.
Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This book will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. Recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer will be included
This book serves as a tribute to the work of the many investigators who have attempted to understand the role of the androgen receptor (AR) in the development and progression of prostate cancer. The relationship between prostate cancer and androgen status was initially appreciated in the late 1800’s, and then awareness reawakened in the 1940’s by the studies of Charles Huggins and colleagues, for which the Nobel prize was awarded in 1966.
The purpose of this book is to provide an up to date review of the molecular and cellular aspects of androgen action in prostate cancer. It includes an overview of the role of androgens in the development of the normal prostate and progression of prostate cancer. Our understanding of androgen metabolism and efforts to target androgen metabolism in the prevention and treatment of prostate cancer is presented. Androgen receptor structure/function relationships and the role of co-regulators are defined. Ligand-independent activation of the androgen receptor and the role of the androgen receptor during progression to the castration recurrent phenotype are discussed. Androgen-regulated genes are elucidated and their roles during prostate cancer progression are defined. Finally, the androgen receptor is presented as a viable target for novel therapies. Together, these reviews should give the reader a comprehensive conceptual framework of androgen action in prostate cancer.
