Antineoplastic Action of Growth Hormone-Releasing Hormone (GHRH) Antagonists
Pp. 530-551 (22)
Agnieszka Siejka, Hanna Lawnicka, Gabriela Melen-Mucha, Ewelina Motylewska, Jan Komorowski and Henryk Stepien
Some growth hormone-releasing hormone (GHRH) antagonists are able to
inhibit the growth of various experimental human cancers. The antitumor effects of first
antagonists seemed to be dependent mainly on the disruption of pituitary secretion of
growth hormone (GH), followed by a reduction in the levels of circulating insulin-like
growth factor (IGF)-1, an important growth factor for cancer cells. It seems obvious that
growth hormone deficiency (GHD) induced by GHRH antagonists, with all its
complications, could limit the beneficial effects of GHRH antagonist therapy, and decrease
the quality of life of the patient. The discovery of local autocrine/paracrine production of
GHRH and other related growth factors in many tumoral tissues, together with that of the
wide expression of GHRH receptors on cancer cells, have directed research to the synthesis
of more potent GHRH antagonists. These compounds exert strong inhibitory effects
directly on tumor growth, with scarce endocrine action. The receptor-mediated mechanisms
are complex and still not completely understood, and involve various intracellular signaling
pathways strictly related to human tumorigenesis. This chapter summarizes the recent
patents and latest observations on the antineoplastic role of GHRH antagonists in human
tumors with an emphasis on the potential therapeutic applications for clinical oncology.
Acromegaly, AMPK, angiogenesis, benign prostatic hyperplasia,
breast cancer, cancer therapy, GHRH, GHRH analogs, GHRH antagonists, GHRH
receptors, IGF-I, IGF-II, intracellular pathway, janus kinase, lung cancer, MAPK,
neuropeptides, oncology, PACAP, prostate cancer, tumor growth.
Department of Immunoendocrinology, Chair of Endocrinology, Medical University of Lodz, ul. Sterlinga 3, 91-425, Lodz, Poland.