A growing body of research reveals that growth hormone (GH), long known for its role in growth and development, may have a darker side — one that could be manipulated for therapeutic benefit in cancer. A comprehensive review published in Endocrine Reviews spotlights the role of GH in cancer development and progression and evaluates the promise of GH-targeted therapies.
The pituitary gland traditionally produces GH. However, this new review challenges conventional narratives by detailing how GH is also produced locally in non-pituitary tissues, including tumors. In these sites, GH functions in autocrine and paracrine modes, acting directly on tumor cells or neighboring cells within the tumor microenvironment. The authors argue that this localized GH activity can support tumor survival, proliferation, angiogenesis, and metastasis. “Hundreds of studies across >20 different cancer types over the last 70 years have amassed a persuasive body of evidence implicating GH and cancer,” they write, emphasizing that “GH as a cellular growth factor (autocrine/paracrine action) in cancer is more relevant than that of GH as a hormone (endocrine action).”
This paradigm-shifting concept — that GH is not merely a systemic growth signal but also a local promoter of oncogenesis — has significant implications. The review carefully outlines the mechanisms by which GH drives cancer biology. Key among them is GH’s activation of the growth hormone receptor (GHR), which in turn modulates several downstream pathways, including the JAK2/STAT5, MAPK, and PI3K/AKT pathways. These signaling cascades are well-known contributors to oncogenic processes, such as unchecked cell proliferation and resistance to cell death or apoptosis.
The GH/IGF-1 axis is also scrutinized. IGF-1 (insulin-like growth factor 1), produced in response to GH stimulation, is itself a potent growth factor implicated in cancer. The interaction between GH, IGF-1, and their respective receptors can amplify tumor-promoting signals. Notably, this axis is already a target of interest in some cancer therapies, but this review suggests a need to look beyond IGF-1 alone and directly at GH and GHR as intervention points.
Of particular concern are patients with conditions that involve elevated GH levels, such as acromegaly, or those receiving GH therapy for growth deficiencies. In these populations, the risk of GH-fueled tumor growth may be elevated, especially in the context of pre-existing cancer susceptibility. The authors call for more nuanced approaches in monitoring and managing such patients.
Encouragingly, the review also highlights ongoing efforts to develop GH-targeted therapies. These include GHR antagonists such as pegvisomant, as well as newer molecular agents that inhibit GH binding or downstream signaling. While still in early phases, such strategies may prove effective in slowing or reversing tumor progression in GH-sensitive cancers. By reframing GH from a purely growth-promoting hormone to a possible oncogenic driver, this review opens new avenues for precision medicine. Targeting GH action, especially its local effects in tumors, could one day form part of a multi-pronged approach to cancer treatment — one that goes beyond traditional chemotherapeutics and targets the very signals that sustain malignancy.
Loading ...