Downregulation of IGFBP2 is associated with resistance to IGF1R therapy in rhabdomyosarcoma.

ABSTRACT: Agents targeting the insulin-like growth factor-1 receptor (IGF1R) are in clinical development, but, despite some initial success of single agents in sarcoma, response rates are low with brief durations. Thus, it is important to identify markers predictive of response, to understand mechanisms of resistance, and to explore combination therapies. In this study, we found that, although associated with PAX3-FKHR translocation, increased IGF1R level is an independent prognostic marker for worse overall survival, particularly in patients with PAX3-FKHR-positive rhabdomyosarcoma (RMS). IGF1R antibody-resistant RMS cells were generated using an in vivo model. Expression analysis indicated that IGFBP2 is both the most affected gene in the insulin-like growth factor (IGF) signaling pathway and the

SUBMITTER: Kang Z 

PROVIDER: S-EPMC7667493 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature