Dysregulation of the PRUNE2/PCA3 genetic axis in human prostate cancer: from experimental discovery to validation in two independent patient cohorts.

Background: We have previously shown that the long non-coding (lnc)RNA (; formerly ) functions as a trans-dominant negative oncogene by targeting the previously unrecognized prostate cancer suppressor gene (a homolog of the gene), thereby forming a functional unit within a unique allelic locus in human cells. Here, we investigated the / regulatory axis from early (tumorigenic) to late (biochemical recurrence) genetic events during human prostate cancer progression.

Methods: The reciprocal and gene expression relationship in paired prostate cancer and adjacent normal prostate was analyzed in two independent retrospective cohorts of clinically annotated cases post-radical prostatectomy: a single-institutional discovery cohort (n=107) and a multi-institutional validation cohort (n=497).

Survival outcomes for advanced kidney cancer patients in the era of targeted therapies.

Background: Advanced renal cell carcinoma (RCC) results in over 14,000 deaths each year in the United States alone. The therapeutic landscape for advanced RCC changed dramatically with the approval of tyrosine kinase inhibitors (TKI) between 2006 and 2012. A large-scale analysis of survival trends has not been performed in the TKI era to determine their impact on outcomes for advanced RCC patients.

Going viral? Linking the etiology of human prostate cancer to the long noncoding RNA and oncogenic viruses.

The hypothesis is discussed that prostate cancer marker lncRNA was introduced into the human genome by an oncogenic virus, and that viral infection‐related mechanisms might underlie its overexpression and prostate cancer initiation and/or progression. [Image: see text]

Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.

Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients.

PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3.

Prostate cancer antigen 3 (PCA3) is the most specific prostate cancer biomarker but its function remains unknown. Here we identify PRUNE2, a target protein-coding gene variant, which harbors the PCA3 locus, thereby classifying PCA3 as an antisense intronic long noncoding (lnc)RNA. We show that PCA3 controls PRUNE2 levels via a unique regulatory mechanism involving formation of a PRUNE2/PCA3 double-stranded RNA that undergoes adenosine deaminase acting on RNA (ADAR)-dependent adenosine-to-inosine RNA editing.

Drug design strategies for the treatment of prostate cancer.

Introduction: While metastatic prostate cancer remains an incurable tumor, remarkable progress has been made with novel drug design strategies for this incurable disease. Several new agents, including hormonal analogues, cytotoxic chemotherapy drugs, radionuclides and innovative targeted therapies, have recently been approved by the FDA for use in advanced and/or metastatic castrate-resistant prostate cancer. Furthermore, a growing number of new diagnostic or predictive genetic tests have also been incorporated into the management of this disease.