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

Abstract

In an in vivo tumor model, downregulation of the GH/IGF-I axis significantly reduces meningioma growth and, in some instances, causes tumor regression. Because the concentrations of IGF-II in tumor did not vary with pegvisomant treatment and there was no autocrine IGF-I production by the tumors, the mechanism of the antitumor effect is most likely a decrease of IGF-I in the circulation and/or surrounding host tissues. Because the authors have previously demonstrated that the GH receptor is ubiquitously expressed in meningiomas, direct blockade of the GH receptor on the tumors may also be contributing to inhibitory actions.

Targeting insulin-like growth factor pathways

“…A pegylated mutant GH (pegvisomant) has been developed to disrupt GH signalling in patients with acromegaly, a condition of GH excess. This compound also has antitumour activity (McCutcheon et al, 2001). While the precise mechanisms for the antitumour activity of these compounds is not completely understood, as both GHRH and GH antagonists may have direct antitumour activity, they both result in suppression of serum IGF-I levels.…”

The Emerging Role of the Insulin-Like Growth Factor Pathway as a Therapeutic Target in Cancer

“…Also, pegvisomant, a pegylated mutant GH, has been developed and approved for the treatment of acromegaly, a condition of GH excess. This compound has antitumor activity in human meningiomas in nude mice [61]. Another strategy that has potential to block both IGF-I as well as IGF-II involves neutralizing monoclonal antibodies and IGFBPs, as demonstrated in breast cancer [62] and prostate cancer [63] models.…”

Growth hormone, insulin-like growth factor system and carcinogenesis

“…Treatment of WT FVB/N mice with pegvisomant severely reduced mammary development and reduced GH and IGF-I signalling in mammary glands. The ability of pegvisomant to inhibit cancer growth was also investigated in human colorectal carcinoma cell lines in nude mice [46]. In this study, Colo205 and HT-29 cell xenographs were grown in nude mice until they reached a volume of 90-105 mm 3 and 60-70 mm 3 , respectively.…”