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.