Current Drug Targets - Volume 14, Issue 4, 2013

Androgens and the androgen receptor have been the focus of prostate cancer research since the early 1940s, when Huggins and Hodges demonstrated that removal of androgens caused advanced prostate cancer to regress. Since that time, a large number of androgen deprivation therapies have been developed in an effort to cure this disease, but prostate cancer remains one of the leading causes of cancer death Read More

The growth and dependence of Prostate Cancer (PCa) on androgen stimulation led to the use of castration to reduce circulating levels of androgens and anti-androgens to directly target the androgen receptor (AR) ligand-binding domain (LBD). However, castration-resistant prostate cancer (CRPC) resistant to anti-androgens invariably develops and can be associated with AR genomic aberrations (mutations, amplification) an Read More

Prostate cancer (CaP) is the most frequently diagnosed cancer and leading cause of cancer death in American men. Almost all men present with advanced CaP and some men who fail potentially curative therapy are treated with androgen deprivation therapy (ADT). ADT is not curative and CaP recurs as the lethal phenotype. The goal of this review is to apply our current understanding of CaP and castration-recurrent CaP (C Read More

The androgen receptor (AR) is a master regulator transcription factor in normal and cancerous prostate cells. Canonical AR activation requires binding of androgen ligand to the AR ligand binding domain, translocation to the nucleus, and transcriptional activation of AR target genes. This regulatory axis is targeted for systemic therapy of advanced prostate cancer. However, a new paradigm for AR activation in castration-r Read More

DNA damage and genetic rearrangements are hallmarks of cancer. However, gene fusions as driver mutations in cancer have classically been a distinction in leukemia and other rare instances until recently with the discovery of gene fusion events occurring in 50 to 75% of prostate cancer patients. The discovery of the TMPRSS2-ERG fusion sparked an onslaught of discovery and innovation resulting in a delineation of prosta Read More

Androgen receptor activity is essential for prostate cancer development and progression. While there are classically defined roles for the retinoblastoma (Rb) and p53 tumor suppressor pathways in maintenance of cell cycle control and the DNA damage response, recent studies have demonstrated a direct role of these two pathways in regulating AR expression and function. While the role of Pten deregulation in prosta Read More

The androgen receptor (AR) is a steroid hormone receptor that functions as a ligand-dependent transcriptional factor, which plays a key role in the development and progression of prostate cancer. Recent advancement in highthroughput technologies including microarrays and deep-sequencing provides unbiased genome-wide knowledge on the AR signaling including datasets for androgen-regulated gene expression and genomi Read More

Androgen receptor (AR) action is critical for prostate cancer (CaP) progression, but is not inhibited fully by available androgen deprivation therapy (ADT). One of the limitations to current ADT is that it targets all androgen action in CaP, and other, cells irrespective of clinical relevance. The resulting off-target effects are responsible for ADTassociated side effects that affect negatively a patient's quality of life. Isolation of the Read More

Diabetic nephropathy (DN) continues being the primary cause of chronic hemodialysis and terminal renal disease worldwide. At tissue levels the DN occurs with glomerulopathy affecting the integrity of the filtration barrier and with an extensive glomerular and tubule-interstitial fibrosis. Current available therapeutic approaches have only demonstrated a modest effect on progression of kidney injury. Therefore, more research co Read More

Ischemic stroke is the leading cause of mortality and morbidity worldwide for which the assemblage of therapeutic interventions has remained outstandingly limited. Several new insights into the causes of neuronal death during ischemic event have led to the identification of some important novel targets for intervention. This article highlights some of the promising protein targets, which are in the validation process and have Read More

A wealth of preclinical and clinical literature has established functional associations of CNS dopamine (DA) and its multiple G protein-coupled receptor (GPCR) types in the integration of key neurological processes linked to complex behavioral activities. Conversely, an equivalent vast literature supports the role of aberrant CNS DA expression and DA receptor signaling in the etiology and persistence of major psychiatri Read More