Targeting of insulin-like growth factor type 1 receptor in Ewing sarcoma: unfulfilled promise or a promising beginning?

摘要

The selective targeting of oncogenic proteins and its translation into disease-specific clinical trials have largely driven the effort to identify new, singular targets that can be exploited for cancer therapy. Targeting the insulin-like growth factor type 1 receptor (IGF-1R) in Ewing sarcoma (ES) and the Ewing Sarcoma Family of Tumors (ESFT) certainly looked to fit the bill: a strong biologic rationale with a disease-defining translocation dependent on IGF signaling for transformation, preclinical evidence of antitumor effects with IGF-1R inhibition, and even impressive signals of clinical activity with IGF-1R inhibitors from early phase I studies. Yet in the accompanying articles, Pappo et al1 and Juergens et al2 report relatively disappointing results from two phase II trials evaluating IGF-lR-targeting monoclonal antibodies (R1507 [Roche, Basel, Switzerland] and figitumumab [Pfizer, New London, CT]), in which the treatment of 222 patients resulted in modest overall response rates (10% with R1507 and 14.2% with figitumumab) and poor median progression-free survival (1.3 months with R1507 and 1.9 months with figitumumab). We are now left with the same question with which we started: What is the potential of IGF-1R targeting for cancer therapy?