ABSTRACT Gonadotropin-releasing hormone (GnRH) analogues are the preferred treatment for advanced and even metastatic or recurring carcinomas. The original rationale for a GnRH analogue in the treatment was to block the endogenous gonadotropin (and thereby steroid hormone) secretion which were thought to stimulate tumor growth. However, the analogues inhibit proliferation of GnRH receptor-bearing tumor cells both in vivo and in vitro, supporting a evidence for a direct antiproliferative effect. GnRH agonists induce initial stimulation of gonadotropin release and subsequent sex steroid release, after some time followed by chemical hypophysectomy, while antagonists cause an immediate and rapid suppression of gonadotropin secretion. Therefore the GnRH antagonists are superior in the treatment of gonadotropin and steroid-dependent disorders. In addition to the anticancer action, GnRH analogues act to protect the gonads during radiation and/or chemotherapy by preferentially steering cells into cell cycle arrest with a decline in responsibility to the chemotherapy and radiation. Some tumoricidal agents linked to analogs of GnRH will also applications for targeted chemotherapy of certain GnRH receptor-bearing tumors. These favoufable effects may raise the advantage of GnRH antagonists in anticancer management.
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