Commentary RE: Upregulation of PSMA Following Androgen Deprivation Therapy

  • Warren D.W. Heston
    Address correspondence to: George L. Wright, Jr, PhD, Department of Microbiology and Immunology, Eastern Virginia Medical School, 700 Olney Road, Norfolk, VA 23501.
    Glickman Urological Institute and Department of Cancer Biology Lerner Research Institute, Cleveland Clinic
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      The seminal and highly cited article by George L. Wright and collaborators that described the upregulation of prostate specific membrane antigen (PSMA) in Urology in 1996 was one of a number of articles in which he and colleagues provided important clinical correlations for the role of PSMA as a target for imaging and therapy.
      • Wright Jr., GL
      • Grob BM
      • Haley C
      • et al.
      Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
      Using human specimens obtained before and after therapy and a quantitative immunostaining procedure that included the number of cells expressing the marker and the intensity of that staining, they observed an increase in PSMA expression in 55% (11 of 21) of primary prostate carcinoma specimens and 100% (4 of 4) of post-treatment metastatic specimens. This finding contrasted dramatically with immunostaining for PSA, which decreased in nearly all specimens and led them to conclude that PSMA was upregulated as a target with androgen deprivation therapy and it did not seem to matter which type of deprivation therapy at that time was used. Notably, one sample that exhibited increased PSA expression following therapy correspondingly showed a decrease in PSMA expression. They also tested the LNCaP cell line in vitro and experimentally determined that removing androgen from the culture media led to increased PSMA protein whereas androgen supplementation led to a decrease in PSMA protein.
      • Wright Jr., GL
      • Grob BM
      • Haley C
      • et al.
      Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
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        • Wright Jr., GL
        • Grob BM
        • Haley C
        • et al.
        Upregulation of prostate-specific membrane antigen after androgen-deprivation therapy.
        Urology. 1996; 48: 326-334
        • Troyer JK
        • Feng Q
        • Beckett ML
        • Wright Jr., GL
        Biochemical characterization and mapping of the 7E11-C-5.3 epitope of the prostate-specific membrane antigen.
        Urol Oncol. 1995; 1: 29-37
        • O'Keefe DS
        • Bacich DJ
        • Huang SS
        • Heston WDW
        A perspective on the evolving story of PSMA biology, PSMA-based imaging, and endoradiotherapeutic strategies.
        J Nucl Med. 2018; 59: 1007-1013
        • Hoffmann MA
        • Wieler HJ
        • Baues C
        • Kuntz NJ
        • Richardsen I
        • Schreckenberger M
        The impact of 68Ga-PSMA PET/CT and PET/MRI on the management of prostate cancer.
        Urology. 2019; 130: 1-12
        • Hoffman MS
        • Violet J
        • Hicks RJ
        • et al.
        177-Lu-PSMA617 radionuclide treatment in patients with metastatic castration resistant prostate cancer (LuPSMA trial): a single arm phase 2 study.
        Lancet Oncol. 2018; (Available at:)
        • Hoffman MS
        • Emmett L
        Tumour heterogeneity and resistance in prostate cancer: a fundamental limitation of prostate-specific membrane antigen theranostics or a key strength ?.
        Eur Urology. 2019; (Available at:)
        • Aggarwal R
        • Wei X
        • Kim W
        • et al.
        Heterogenous flare in prostate-specific membrane antigen positron emission tomography tracer uptake with initiation of androgen blockade in prostate cancer.
        Eur Urol Oncol. 2018; 1: 78-82
        • Calais J
        • Ceci F
        • Eiber M
        • et al.
        18-F fluciclovine PET-CT and 68-Ga PSMA-11 PET-CT in patients with early biochemical recurrence after prostatectomy: a prospective, single –center, single arm, comparative imaging trial.
        Lancet Oncol. 2019; (Available at:)
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