The insulin-like growth factor (IGF) pathway is a complex pathway involving interactions between membrane-bound receptors, ligands, binding proteins, downstream effectors, and other receptor @entity4149 kinase signaling cascades. The IGF pathway has been identified as a potential therapeutic target in @entity1149 ( @entity1149 ) based on the following provocative factors. Preclinical observations in @entity1149 have shown that this pathway is involved in @entity5 cell proliferation, survival, and invasiveness. In addition, @entity2856 protein expression is found in a significant number of non-small cell @entity5 specimens. Initial therapeutic efforts involved the development of monoclonal antibodies and @entity4149 kinase inhibitors that target @entity2856 , a transmembrane receptor @entity4149 kinase. Enthusiasm for targeting this pathway increased when a randomized phase II study showed that combining an anti- @entity2856 monoclonal antibody (figitumumab) with a @entity902 doublet resulted in a higher response rate and trends for superior progression-free survival and overall survival. Subsequently, a phase III study failed to confirm the promising results observed in the phase II trial. Currently, investigators are studying different monoclonal antibodies and @entity4149 kinases targeting @entity2856 . In unselected @entity1 , results presented thus far do not suggest efficacy of this agent. However, retrospective subgroup analyses suggest that circulating @entity442 levels might identify @entity1 who could benefit from treatment with an @entity2856 monoclonal antibody and may warrant further exploratory studies for predictive molecular markers. The purpose of this paper is to briefly discuss the IGF pathway and its relationship with other signaling pathways in @entity2 and to review the ongoing IGF clinical trials and efforts to identify predictive molecular markers.

Targeting the insulin-like growth factor receptor pathway in XXXX : problems and pitfalls.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small cell lung cancer'] @entity442 :: ('3479', 'Gene') :: ['IGF-1'] @entity2 :: ('MESH:D008175', 'Disease') :: ['lung cancer'] @entity2856 :: ('3480', 'Gene') :: ['IGF-1R'] @entity4149 :: ('D014443', 'Chemical') :: ['tyrosine'] @entity902 :: ('MESH:D010984', 'Chemical') :: ['platinum']
@entity2 :: (MESH:D008175,Disease) :: ['lung cancer']
