title: The prostate-specific membrane antigen: lessons and current clinical implications from 20 years of research.
abstract: OBJECTIVE
  Despite a multitude of detection and treatment advances in the past 2 decades, prostate cancer remains the second leading cause of deaths due to cancer among men in the United States. Technological evolution and expanding knowledge of tumor biomarkers have invigorated exploration in prostate cancer therapeutics. Prostate-specific membrane antigen (PSMA) was one of the first prostate cancer biomarkers successfully cloned. Since then, it has been characterized as the prototypical cell-surface marker for prostate cancer and has been the subject of intense clinical inquiry. In this article, we review the relevant research in PSMA on the 20th anniversary of its cloning.
  
  
  METHODS
  A PubMed search using the keywords "prostate-specific membrane antigen" or "glutamate carboxypeptidase II" provided 1019 results. An additional 3 abstracts were included from scientific meetings. Articles were vetted by title and abstract with emphasis placed on those with clinically relevant findings.
  
  
  RESULTS
  Sixty articles were selected for inclusion. PSMA was discovered and cloned in 1993. Its structure and function were further delineated in the ensuing decade. Consensus sites of expression in normal physiology are prostate, kidney, nervous system, and small intestine. PSMA has been implicated in the neovasculature of several tumors including urothelial and renal cell carcinomas. In prostate cancer, expression of PSMA is directly related to the Gleason grade. PSMA has been tested both in imaging and therapeutics in a number of prostate cancer clinical trials. Several recent approaches to target PSMA include the use of small molecule inhibitors, PSMA-based immunotherapy, RNA aptamer conjugates, and PSMA-targeted prodrug therapy. Future study of PSMA in prostate cancer might focus on its intracellular functions and possible role in tumor neurogenesis.
  
  
  CONCLUSIONS
  Twenty years from its discovery, PSMA represents a viable biomarker and treatment target in prostate cancer. Research to delineate its precise role in prostate carcinogenesis and within the therapeutic armamentarium for patients with prostate cancer remains encouraging.
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors: Benjamin T
authors: BT
authors: Ristau
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA. Electronic address: okeeds@upmc.edu.
authors: Denise S
authors: DS
authors: O'Keefe
authors: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
authors: Dean J
authors: DJ
authors: Bacich
mesh_terms: D000954:Antigens, Surface; D014408:Biomarkers, Tumor / Q000032:analysis*; D043425:Glutamate Carboxypeptidase II; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis*
chemical_list: D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II
keywords: Cancer therapeutics; Folate; Prostate cancer; Prostate-specific membrane antigen; Tumor markers