title: Targeting the insulin growth factor pathway in gastrointestinal cancers.
abstract: Insulin-like growth factor 1 (IGF-1)-directed therapy is currently at a crossroads. After decades of research, several agents targeting the IGF pathway are now in clinical trials. One recent phase III trial of the IGF-1R inhibitor figitumumab in patients with non-small-cell lung cancer was discontinued after an interim analysis showed no survival improvement. Clinical trials for patients with sarcoma have demonstrated impressive anti-tumor activity in cases where the IGF-1 pathway is activated, such as in Ewing sarcoma; however, acquired resistance has been common. Recently, randomized phase II trials combining IGF-1 R with epidermal grown factor receptor (EGFR) inhibition in colorectal cancer have been completed. Preclinical studies have indicated that several biomarkers may have potential predictive value. Studies of IGF-1R inhibitors in gastrointestinal cancers are currently ongoing in pancreatic, gastroesophageal, hepatocellular, and colorectal cancers. A critical analysis of prior work in this field and a rational strategy for maximizing success on the basis of biomarker use are necessary.
authors: Sheba Medical Center, Tel Hashomer, Israel.
authors: Talia
authors: T
authors: Golan
authors: Milind
authors: M
authors: Javle
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D005770:Gastrointestinal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D014408:Biomarkers, Tumor; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1