IGF-1R targeted treatment of sarcoma.

摘要

The first study to report in-vitro responses of a Ewing's sarcoma cell line to type 1 insulin-like growth factor (IGF-1) was published 20 years ago, and was quickly followed by additional cell-line studies that showed modulation of chemosensitivity by IGF-1.1 At this time, the IGF-1-initiated signalling pathways were just beginning to be resolved and the goals of using IGF-1 involved maintaining cell viability in a serum-free environment.1 The alR3 antibody, which was developed to block activation of the IGF-1 receptor (IGF-1R), inhibited most Ewing's sarcoma cell lines andxenografts. Additional evidence also supported the importance of IGF-1 signalling in Ewing's sarcoma: the requirement of IGF-1R for EWS-FLI1 transformation, a possible role for high IGF-1 levels in chemotherapy resistance, and the transcriptional repression of IGF-binding-protein-3 by EWS-FLI1. This 20-year accumulation of research strongly suggested that clinical inhibition of IGF-1R would be beneficial for patients with Ewing's sarcoma.