title: Targeting the IGF-1R: The Tale of the Tortoise and the Hare.
abstract: The insulin-like growth factor type 1 receptor (IGF-1R) plays a key role in the development and maintenance of cancer. Since the first links between growth factor receptors and oncogenes were noted over three decades ago, targeting the IGF-1R has been of great interest. This review follows the progress from inception through intense pharmaceutical development, disappointing clinical trials and recent updates to the signaling paradigm. In light of major developments in signaling understanding and activation complexities, we examine reasons for failure of first line targeting approaches. Recent findings include the fact that the IGF-1R can signal in the absence of the ligand, in the absence of kinase activity, and utilizes components of the GPCR system. With recognition of the unappreciated complexities that this first wave of targeting approaches encountered, we advocate re-recognition of IGF-1R as a valid target for cancer treatment and look to future directions, where both research and pharmaceutical strengths can lend themselves to finally unearthing anti-IGF-1R potential.
authors.affiliation: Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Caitrin
authors.initials: C
authors.lastname: Crudden
authors.affiliation: Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden ; Department of Dermatology, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Ada
authors.initials: A
authors.lastname: Girnita
authors.affiliation: Department of Oncology and Pathology, Cancer Centre Karolinska, Karolinska Institutet, Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Leonard
authors.initials: L
authors.lastname: Girnita
keywords: GPCR; IGF-1R; RTK; biased signaling; cancer