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Free Content Clinical Trials of Cancer Therapies Targeting Prostate-Specific Membrane Antigen

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Prostate cancer is the most common non-cutaneous cancer of men in the United States and represents their second-leading cause of cancer-related death. Metastatic disease is largely resistant to conventional chemotherapies, and targeted therapies are urgently needed. Prostate-specific membrane antigen (PSMA) is a prototypical cell-surface marker of prostate cancer. PSMA is an integral, nonshed, type 2 membrane protein with abundant and nearly universal expression in prostate carcinoma, but has limited extra-prostatic expression. In addition, PSMA is expressed in the neovasculature of other solid tumors. These findings have spurred development of PSMA-targeted therapies for cancer, and first-generation products have entered clinical testing. Vaccine approaches have included recombinant protein, nucleic acid and cell-based strategies, and anti-PSMA immune responses have been demonstrated in the absence of significant toxicity. Therapy with drug-conjugated and radiolabeled antibodies has yielded objective clinical responses as measured by reductions in serum prostate-specific antigen and/or imageable tumor volume. However, responses were observed in a minor fraction of patients and at doses near the maximum tolerated dose. Overall, these initial studies have provided measured proof of concept for PSMAbased therapies, and second-generation antibody and vaccine products may hold the key to exploit PSMA for molecularly targeted therapy of prostate and other cancers.





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Keywords: Prostate-specific membrane antigen; antibody-drug conjugate; immunotherapy; prostate cancer

Document Type: Research Article

Publication date: September 1, 2007

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  • Reviews on Recent Clinical Trials publishes frontier reviews on recent clinical trials of major importance. The journal's aim is to publish the highest quality review articles in the field. Topics covered include: important Phase I - IV clinical trial studies, clinical investigations at all stages of development and therapeutics.

    The journal is essential reading for all researchers and clinicians involved in drug therapy and clinical trials.
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