Peptide analogs in the therapy of prostate cancer

• Published in: The Prostate Vol. 45; no. 2; pp. 158 - 166
• Main Authors: Schally, Andrew V., Comaru-Schally, Ana Maria, Plonowski, Artur, Nagy, Attila, Halmos, Gabor, Rekasi, Zoltan
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01-10-2000; Wiley-Liss
• Subjects: agonists of LH-RH; and somatostatin or cytotoxic peptide analogs; Androgens - metabolism; Animals; antagonists of LH-RH; Biological and medical sciences; bombesin; Bombesin - analogs & derivatives; Bombesin - antagonists & inhibitors; bombesin antagonists; Cytotoxins - pharmacology; Gastrin-Releasing Peptide - analogs & derivatives; Gastrin-Releasing Peptide - antagonists & inhibitors; GH-RH antagonists; Gonadotropin-Releasing Hormone - agonists; Gonadotropin-Releasing Hormone - analogs & derivatives; Gonadotropin-Releasing Hormone - antagonists & inhibitors; Humans; Male; Medical sciences; Other treatments; Peptides - chemistry; Peptides - therapeutic use; Prostatic Neoplasms - drug therapy; Somatostatin - analogs & derivatives; targeted cytotoxic analogs of LH-RH; targeted cytotoxic analogs of LH‐RH, bombesin, and somatostatin or cytotoxic peptide analogs; Treatment. General aspects; Tumors; Human; Hormone; Agonist; Urinary system disease; Bombesin; Prostate disease; Peptide hormone; Cytotoxicity; Tumoral marker; Gonadotropin; Malignant tumor; Glycoprotein hormone; Neuropeptide; Prostate specific antigen; Pituitary hormone; Treatment; Adenohypophyseal hormone; Luteinizing hormone; Antagonist; Somatostatin; Male genital diseases; Prostate
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/1097-0045(20001001)45:2<158::AID-PROS10>3.0.CO;2-K

The use of peptide analogs in the therapy of prostate cancer is reviewed. The preferred primary treatment of advanced androgen‐dependent prostate cancer is presently based on the use of depot preparations of LH‐RH agonists. This treatment is likewise recommended in patients with rising PSA levels after surgery or radiotherapy. LH‐RH agonists with or without antiandrogens can be also utilized prior to or following various local treatments in patients with clinically localized prostate cancer and at high risk for disease recurrence. LH‐RH antagonists like Cetrorelix are in clinical trials. However, most patients with advanced prostatic carcinoma treated by any modality of androgen deprivation eventually relapse. Treatment of relapsed androgen‐independent prostate cancer remains a major challenge, but new therapeutic modalities are being developed based on antagonists of growth hormone‐releasing hormone (GH‐RH) and bombesin, which inhibit growth factors or their receptors. Another approach consists of cytotoxic analogs of LH‐RH, bombesin, and somatostatin containing doxorubicin or 2‐pyrrolinodoxorubicin, which can be targeted to receptors for these peptides found in prostate cancers and their metastases. These cytotoxic analogs inhibit growth of experimental androgen‐dependent or ‐independent prostate cancers and reduce the incidence of metastases. A rational therapy with peptide analogs could be selected on the basis of receptors present in biopsy samples. The approaches based on peptide analogs should result in a more effective treatment for prostate cancer. Prostate 45:158–166, 2000. © 2000 Wiley‐Liss, Inc.