The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth

  title={The growth hormone receptor antagonist pegvisomant blocks both mammary gland development and MCF-7 breast cancer xenograft growth},
  author={Jana Divisov{\'a} and Isere Kuiatse and Zawaunyka W Lazard and Heidi L. Weiss and Franzanne Vreeland and Darryl L. Hadsell and Rachel Schiff and Charles Kent Osborne and Adrian V. Lee},
  journal={Breast Cancer Research and Treatment},
SummaryMammary gland development is dependent upon the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis, this same axis has also been implicated in breast cancer progression. In this study we investigated the effect of a GH antagonist, pegvisomant (Somavert®, Pfizer), on normal mammary gland development and breast cancer xenograft growth. Intraperitoneal administration of pegvisomant resulted in a 60% suppression of hepatic IGF-I mRNA levels and upto a 70–80% reduction of serum IGF… 

Insulin-like growth factors, insulin, and growth hormone signaling in breast cancer: implications for targeted therapy.

  • H. BeckwithD. Yee
  • Biology, Medicine
    Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists
  • 2014
Multitargeted blockade of growth factor receptors and their common downstream kinases will be necessary for the successful treatment of breast cancer.

Growth hormone excess promotes breast cancer chemoresistance.

CONTEXT GH and IGF-I are known to promote breast carcinogenesis. Even if breast cancer (BC) incidence is not increased in female acromegalic patients, mortality is greater as compared with general

Growth Hormone Upregulates Mediators of Melanoma Drug Efflux and Epithelial-to-Mesenchymal Transition In Vitro and In Vivo

It is identified that GH upregulates key mechanisms of therapy resistance and metastases in melanoma tumors in an IGF-1 dependent and independent manner by upregulating multidrug efflux pumps and EMT transcription factors.

Role of the growth hormone–IGF-1 axis in cancer

A substantial body of evidence supports a role for the growth hormone–IGF-1 axis in cancer incidence and progression and development of a more potent GH receptor antagonist or secretion inhibitor is warranted for cancer therapy.

Disrupting insulin-like growth factor signaling as a potential cancer therapy

The well-recognized roles of IGF-IR in driving the malignant phenotype are described, the evidence that perhaps IR should also be targeted to inhibit the effects of the IGF ligands and insulin in cancer is examined, and the strategies to disrupt IGF signaling in cancer are described.

Growth hormone and insulin-like growth factor-I in the transition from normal mammary development to preneoplastic mammary lesions.

It is possible that inhibition of IGF-I action, or perhaps GH, in the mammary gland may eventually play a role in breast cancer chemoprevention by preventing actions of both estrogen and progesterone, especially in women at extremely high risk for developing breast cancer such as BRCA gene 1 or 2 mutations.

40 YEARS OF IGF1 Anti-insulin-like growth factor therapy in breast cancer

A review will evaluate the rationale for IGF1R inhibition, discuss results of the clinical trials and suggest a path forward.

Characterization of Growth Hormone Signaling in the NCI60 Cancer Panel

A novel action of GH is discovered: an ability to increase the bioenergetic potential and potentiate the Warburg effect in cancer cells, which may have relevance to growth and invasion of metastatic melanoma cells in vivo.

Growth hormone, insulin-like growth factor system and carcinogenesis.

While ample experimental evidence supports a role of the GH-IGF system in tumour promotion and progression, the strength of evidence from patients with acromegaly, GH deficiency, or treated with GH is much weaker.



Reduced growth of human breast cancer xenografts in hosts homozygous for the lit mutation.

The results suggest that patient-to-patient variability in GH-IGF-I physiology may contribute to the large variability between patients regarding breast cancer behavior, and motivate clinical trials of novel hormonal treatment strategies that target the GH- IGF-I axis.

Growth hormone receptor antagonist administration inhibits growth of human colorectal carcinoma in nude mice.

A central role for the GH/IGF system in the pathogenesis of some colorectal cancers is demonstrated and it is suggested that specific GHR blockade may present a new concept in the treatment of coloreCTal cancer.

Antitumor activity of the growth hormone receptor antagonist pegvisomant against human meningiomas in nude mice.

In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression.

Cross Talk Between Estrogen Receptor and IGF Signaling in Normal Mammary Gland Development and Breast Cancer1

This review will focus on the evidence indicating cross-talk between estrogen and IGF-I and reveal some of the complex mechanisms that link these important pathways in breast cancer.

Cross talk between estrogen receptor and IGF signaling in normal mammary gland development and breast cancer.

This review will focus on the evidence indicating cross-talk between estrogen and IGF-I and reveal some of the complex mechanisms that link these important pathways in breast cancer.

Circulating insulin-like growth factor-I levels regulate colon cancer growth and metastasis.

The hypothesis that circulating IGF-I levels play an important role in tumor development and metastasis in a mouse model of colon cancer is supported.

Evidence that the growth hormone receptor mediates differentiation and development of the mammary gland.

It is shown that nonlactogenic rat (r) GH is far more potent than rPRL in inducing rat mammary development, suggesting that GH receptors play a central role in this process.

Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors.

It is demonstrated that circulating IGF-I levels play a significant role as a risk factor in the onset and development of mammary tumors in two well-established animal models of breast cancer.

The effects of insulin-like growth factors on tumorigenesis and neoplastic growth.

The function and regulation of expression of the IGFs, their receptors and the IGF-binding proteins (IGFBPs), and a number of investigational interventional strategies targeting the GH or IGFs are reviewed.

Targeted disruption of the IGF-I receptor gene decreases cellular proliferation in mammary terminal end buds.

It is indicated that pregnancy-dependent compensatory mechanisms can stimulate mammary development in the absence of an IGF-IR, and this study directly establishes a proliferation-dependent role for the IGF- IR in the cells of the TEB.