Growth Hormone Action as a Target in Cancer: Significance, Mechanisms and Possible Therapies

Growth hormone (GH) is a pituitary derived endocrine hormone required for normal post-natal growth and development. Hypo or hypersecretion of endocrine GH results in two pathologic conditions, namely GH deficiency (GHD) and acromegaly. Additionally, GH is also produced in non-pituitary and tumoral tissues where it acts rather as a cellular growth factor with an autocrine/paracrine mode of action. An increasingly persuasive and large body of evidence over the last 70 years concur that GH action is implicit in escalating several cancer-associated events, locally and systemically. This pleiotropy of GH's effects is puzzling, but the association with cancer-risk automatically raises a concern for patients with acromegaly and for individuals treated with GH. By careful assessment of the available knowledge on the fundamental concepts of cancer, suggestions from epidemiological and clinical studies, and the evidence from specific reports, in this review we aimed to help clarify the distinction of endocrine vs. autocrine/paracrine GH in promoting cancer and reconcile the discrepancies between experimental and clinical data. Along this discourse, we critically weigh the targetability of GH action in cancer - firstly by detailing the molecular mechanisms which posit GH as a critical node in tumor circuitry, and secondly, by enumerating the currently available therapeutic options targeting GH action. On the basis of our discussion, we infer that a targeted intervention on GH action in the appropriate patient population can benefit a sizeable subset of current cancer prognoses.