Urologic Oncology: Seminars and Original Investigations
Review articleThe prostate-specific membrane antigen: Lessons and current clinical implications from 20 years of research
Section snippets
Objectives
Prostate cancer is the most prevalent noncutaneous malignancy in men in the United States and remains the second leading cause of deaths due to cancer in this population [1]. Recently, as a result of well-publicized large randomized controlled trials [2], [3], the use of prostate-specific antigen (PSA) as a screening tool has come under fire. This has culminated in the publication of guidelines aimed at reducing or in some cases eliminating the use of PSA as a screening tool for prostate cancer
Materials and methods
A PubMed search using the keyword āprostate-specific membrane antigenā or āglutamate carboxypeptidase type IIā yielded 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. Articles not written in English were excluded. A total of 85 articles were selected based on abstract and the full text was read in entirety. From this, 60 articles were selected for inclusion
Discovery, structure, and physiology of PSMA
PSMA was first cloned in 1993 [7]. Since then, it has been shown to be identical to both folate hydrolase 1 found at the jejunal brush border and N-acetyl-alphaālinked acidic dipeptidase (NAALADase) in the nervous system [8]. The multiple names have led some to argue for standardization of nomenclature based on function (e.g., glutamate carboxypeptidase type II), however, this has not been widely accepted. Regardless of name, PSMA is a type II transmembrane protein with an N-terminal
Conclusions
PSMA remains an attractive target for the detection, diagnosis, and treatment of prostate cancer 20 years from the date of its cloning. Therapeutics based on it biological role in the nervous system where it functions as an NAALADase are promising in preclinical models. There has yet to be a clinically important effect on survival in patients as a result of PSMA-based therapeutics in prostate cancer. However, several recent new approaches to target PSMA including the use of small molecule
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