Keller G et al. (2005) Effective treatment of experimental human non-Hodgkin's lymphomas with antagonists of growth hormone-releasing hormone. Proc Natl Acad Sci USA 102: 10628–10633

Growth-hormone-releasing hormone (GHRH) gene expression is deregulated in several hematologic malignancies. Furthermore, GHRH antagonists have antitumor effects in many cancer models. These are thought to be mediated indirectly by suppressing hepatic production of insulin-like growth factor I (IGF-I) or directly by actions on the tumor cells. Keller et al. evaluated whether GHRH antagonists can inhibit non-Hodgkin's lymphoma (NHL).

Athymic (nude) mice bearing xenografts of the human NHL cell lines, RL or HT, were treated with the GHRH antagonists, MZ-5-156 or MZ-J-7-138. As measured by tumor volume, this treatment inhibited tumor growth in vivo by up to 74%. A similar effect on proliferation was observed in vitro when NHL cell lines were exposed to the drugs, although the effect of MZ-5-156 was inferior to that of MZ-J-7-138 at lower concentrations.

Both cell lines expressed GHRH and the IGF-I-receptor. The GHRH-receptor splice variant 1 was also expressed, and provided a high-affinity binding site for the radiolabeled GHRH antagonist, JV-1-42. Treatment of nude mice with GHRH antagonists resulted in reduced levels of serum and liver IGF-I in the presence of MZ-5-156 but not MZ-J-7-138. In RL-derived and HT-derived tumors, both antagonists suppressed basic fibroblast growth factor, but had no effect on vascular endothelial growth factor.

The authors suggest that GHRH antagonists exert their antitumor affects directly, by GHRH receptor occupancy, and speculate that these drugs could offer a potential therapy for NHL.