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The decapeptide GnRH (Gonadotropin-Releasing Hormone), whose amino acidic sequence was discovered by Dr. A.V. Schally, was initially identified as the key hypothalamic hormone involved in the control of reproductive functions. GnRH, by binding to specific receptors (GnRH-R) at the pituitary level, stimulates the synthesis and secretion of the two gonadotropins (LH, luteinizing hormone and FSH, follicle stimulating hormone) and the downstream production of steroid hormones at the gonadal level. At present, these receptors represent the molecular targets of the standard pharmacological treatments for hormone-related tumors, such as androgen-dependent prostate cancer. Actually, chronic administration of synthetic GnRH agonists induces the desensitization of pituitary receptors and, subsequently, the suppression of testicular androgen production. The physiological role of GnRH in reproductive functions, and its regulation, represented a very important line of research for professor Martini and His colleagues. In the last three decades it has become increasingly clear that GnRH-R are expressed also in a wide range of tumors, both related and unrelated to the reproductive system; in particular GnRH-R are expressed in prostate cancers after development of resistance to androgen ablation therapy (castration resistant prostate cancer, CRPC), a tumor known to be refractory to standard chemotherapy. Activation of these receptors by means of GnRH agonists is associated with a significant antiproliferative/antimetastatic/antiangiogenic activity. These different biological effects at pituitary vs. prostate tissues are related to specific intracellular signal transduction pathways. Based on these observations, tumor GnRH-R are presently considered an effective molecular target for novel therapies (‘targeted’ therapies). In particular, GnRH-based bioconjugates, in which a standard cytotoxic drug is linked to a GnRH analog, have been developed. The rationale for this ‘targeted’ therapy is that the GnRH analog behaves as the targeting moiety by binding to GnRH-R in tumors, thus specifically delivering (targeting) the cytotoxic drug to tumor cells. At the level of tumor cells, the bioconjugate is internalized and degraded at the lysosomal level; in this way the anticancer drug is specifically released into the tumor cells to exert its cytotoxic effects, while sparing normal cells. In conclusion, GnRH-R are expressed not only at the pituitary level but also in a wide range of tumor tissues; these receptors are at present under investigation as an effective molecular target for the development of novel therapeutic strategies.