Abstract
This chapter discusses the development of agonists and antagonists of luteinizing hormone-releasing hormone (LHRH), also known as GnRH, and their clinical uses. Specific receptors for LHRH were first detected on human breast, prostatic, ovarian, endometrial, and pancreatic cancers. Clinical applications of LHRH agonists are based on gradual down-regulation of pituitary receptors for LHRH and inhibition of the pituitary and gonads. LHRH antagonists represent another class of compounds that may be useful for treatment of sex-hormone dependent cancers and various gynecological applications. LHRH antagonists produce an immediate suppression of the secretion of gonadotrophins and sex steroids and thus achieve rapid therapeutic effects. LHRH agonists and antagonists can be used for the treatment of endometriosis, uterine leiomyomas, and in assisted reproduction programs. The preferred primary treatment of advanced androgen-dependent prostate cancer is based on the periodic administration of depot preparations of LHRH agonists. LHRH agonists can be likewise applied for treatment of breast cancer. LHRH antagonists have been successfully tried for therapy of prostate cancer and benign prostatic hypertrophy. Cytotoxic analogs of LHRH AN-152 and AN-207 containing doxorubicin or 2-pyrrolinodoxorubicin that can be targeted to LHRH receptors on tumors have been synthesized and successfully tested in in-vivo experimental cancer models of human prostate, breast, ovarian, and endometrial cancers, and renal cell carcinomas, melanomas, and lymphomas.
