Antitumor effects of analogs of LH-RH and somatostatin: Experimental and clinical studies

A. V. Schally, G. Srkalovic, B. Szende, T. W. Redding, T. Janaky, A. Juhasz, E. Korkut, R. Z. Cai, K. Szepeshazi, S. Radulovic, L. Bokser, K. Groot, P. Serfozo, A. M. Comaru-Schally

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Many clinical approaches for the treatment of hormone-sensitive tumors are being developed based on analogs of LH-RH and somatostatin. Inhibition of the pituitary-gonadal axis forms the basis for oncological applications of LH-RH agonists like [d-Trp6]-LH-RH and new LH-RH antagonists free of edematogenic effects such as [Ac-d-Nal(2)1-d-Phe(4Cl)2-d-Pal(3)3,d-C it6,d-Ala10]-LH-RH (SB-75). Agonists and antagonists of LH-RH have been used in patients with prostate cancer and might be also beneficial for the treatment of breast cancer and ovarian, endometrial and pancreatic carcinomas. Some of the effects of LH-RH analogs can be due to direct action since LH-RH receptors have been found in these cancers. The use of sustained delivery systems based on microcapsules of PLG, makes the treatment more efficacious. Octaeptide analogs of somatostatin such as d-Pys-Tyr-d-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) and related analogs were designed specifically for antitumor activity. These somatostatin analogs, by virtue of having a wide spectrum of activities appear to inhibit various tumors through multiple mechanisms. Direct antiproliferative actions of somatostatin analogs appear to be mediated by specific receptors located on tumor cells. High affinity binding sites for RC-160 and related analogs have been found in human pancreatic, prostate, breast and ovarian cancers and brain tumors such as meningiomas. In vivo administration of analog RC-160 inhibits the growth of Dunning R-3327 prostate cancers in rats, MXT mammary tumors in mice and BOP-induced ductal pancreatic cancers in hamsters. Combination of microcapsules of RC-160 with [d-Trp6]-LH-RH results in synergistic potentiation of the inhibition of these cancers. Somatostatin analog RC-160 and LH-RH antagonist SB-75 are the object of further experimental studies and clinical trials aimed at the exploration of their inhibitory effects on the processes of malignant growth.

Original languageEnglish (US)
Pages (from-to)1061-1067
Number of pages7
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume37
Issue number6
DOIs
StatePublished - Dec 20 1990

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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