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Miscellaneous

Prostate-specific antigen: a diagnostic marker and a tool for targeted delivery of drugs to prostate tumours

Pages 1035-1046 | Published online: 25 Feb 2005
 

Abstract

Prostatic carcinoma is the second most common malignancy in the USA and the second highest cause of cancer related deaths in men. A prostate-specific antigen (PSA) isolated from prostate tissue and seminal fluid, and also detected in blood serum of prostate cancer patients, led to the development of a serum PSA determination method as a diagnostic and prognostic marker for prostate cancer. PSA is an active protease when released by prostatic tissue, either normal or malignant. In serum it is present as an immunologically reactive but enzymatically inactive complex. Both the antigenic and the proteolytic activities of PSA were exploited to deliver cytotoxic agents at or near the prostate tumour tissues. The enzymatic activity released the agent from short peptide conjugates that are specific substrates of PSA. A new polyamine analogue (SL-11093) was found to inhibit the growth of relatively large (200 mm3) human prostate tumours grafted in athymic mice by ~ 90%. It has greatly reduced systemic toxicity compared with other polyamine analogues. The toxicity may be further decreased by attaching the novel polyamine to a monoclonal antibody raised against PSA for targeted delivery to prostate tumours.

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