Abstract
This chapter focuses on potent antagonistic analogs of growth hormone-releasing hormone (GH-RH) in cancer. GHRH antagonists inhibit the growth, tumorigenicity, and metastases of a wide range of human experimental malignancies. GH-RH antagonists bind to pituitary receptors for GH-RH and inhibit the release of GH in vitro and in vivo. The presence of GH-RH ligand was demonstrated in various cancers, suggesting that GH-RH could be an autocrine growth factor. GH-RH antagonists inhibit the growth of various human cancer lines xenografted into nude mice, including breast cancers, prostate cancers, small cell lung carcinomas (SCLC) and non-SCLC, malignant gliomas, renal cell carcinomas, pancreatic cancers, colorectal carcinomas, and lymphomas. These effects of GHRH antagonists could be exerted in part indirectly through inhibition of the secretion of pituitary GH and the resulting reduction in the levels of hepatic IGF-I. However, the principal effect of GH-RH antagonists appears to be the direct suppression of action of the autocrine GHRH and the secretion of IGF-I and IGF-II in tumors, as well as expression of the genes encoding them. These direct effects of GHRH antagonists are exerted on GHRH receptors and their splice variants on tumors. Further development of GH-RH antagonists should lead to potential therapeutic agents for various cancers.
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