Study Reexamines Role of IGF-1R As Therapeutic Target in Ewing Sarcoma

First author Alison O'Neill, then an undergraduate at Georgetown University and now a first-year medical student at Georgetown, and a team of scientists from Johns Hopkins, Boston Children's Hospital, Memorial Sloan-Kettering Cancer Center, and Georgetown's Lombardi Cancer Center (including senior author Dr. Jeffrey Toretsky), have found evidence that the insulin-like growth factor 1 receptor (IGF-1R) may require reevaluation as a therapeutic target in Ewing sarcoma (ES). The group’s findings, published online on January 29, 2013 in the open-access journal Sarcoma, contribute to a growing body of work that calls into question the longstanding high hopes for anti-IGF-1R therapy in light of the actual nature of IGF-1R’s role in Ewing sarcoma biology. The authors noted that IGF-1R has been the subject of more than 20 years of research as a potential therapeutic target in ES. These investigations have included the role of IGF-1R in the initiation of ES, in vitro and in vivo effects of blocking IGF-1R, and the expression of signaling components in patients with ES. As a result of these data, patients with ES were thought to be ideal candidates for therapy directed towards the IGF-1R axis. ES patients were thus enrolled in early clinical trials of humanized monoclonal antibodies against IGF-1R with the expectation of significant antitumor effects. The phase II studies showed objective response rates that ranged from 8 to 15%, with the vast majority being partial responses measured in weeks to months. The authors said that anti-IGF-1R therapy clearly benefits a subset of patients, and it will be essential to find markers to identify those patients most likely to respond.
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