Growth-inhibitory actions of analogues of Luteinizing Hormone Releasing Hormone on tumor cells.

The expression of LHRH and its receptor has been demonstrated in a number of human malignant tumors, including cancers of the breast, ovary, endometrium, and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Dose-dependent antiproliferative effects of LHRH agonists in cell lines derived from these cancers have been observed by various investigators. LHRH antagonists also have marked antiproliferative activity in most of the ovarian, breast, and endometrial cancer cell lines tested, indicating that the dichotomy of LHRH agonists and antagonists might not apply to the LHRH system in cancer cells. Findings from our laboratories suggest that the classical LHRH receptor signal-transduction mechanisms, known to operate in the pituitary, are not involved in the mediation of antiproliferative effects of LHRH analogues in cancer cells. Results obtained by several groups, including ours, instead suggest that LHRH analogues interfere with the mitogenic signal transduction of growth-factor receptors and related oncogene products associated with tyrosine kinase activity. The pharmacological exploitation of these direct antiproliferative actions of LHRH analogues might provide new therapeutic approaches to these cancers.