[The discovery of hypothalamic hormones and the development of antitumor analogs]

Although after the discovery of GnRH, research was initially directed towards the treatment of infertility, the development during the last twenty-five years of synthetic GnRH analogs has led to major advances in the diagnosis and treatment of endocrine disorders and cancer. Agonists are 50-100 times more potent than the natural neuropeptide and induce an intense and constant secretion of gonadotrophins, while their continuous administration induces hypophyseal desensitization with a fall in FSH and LH production leading to a reduction in sex hormones production and therefore chemical castration. This has been used for the treatment of precocious puberty, in vitro fertilization protocols and management of various hormone-dependent cancers such as prostate and breast cancer, a field where these indications are being continually extended. LHRH antagonists, used at doses higher than those of agonists, induce an immediate inhibition of gonadotrophin secretion and rapidly reduce sex steroid levels. Their development is more recent, and they have begun to find a role in prostatic diseases, cancer and benign prostatic hypertrophy. The discovery of GnRH receptors in various types of cancer has suggested a direct cytotoxic effect on cancer cells as well as the indirect hormonal effect. Research currently in the preclinical stage involves the use of combinations of ligand analogs and cytotoxic agents to increase the anti-tumoral specificity of chemotherapy and provide greater efficacy and reduced collateral toxicity. The management strategy of prostate, breast and ovarian cancers may therefore be considerably modified. Likewise, this concept of targeted chemotherapy using analogs acting as cytotoxic agent carriers up to the tumor site is the aim of research to evaluate somatostatin and bombesin.