These results suggested that a lack of N-linked sugars at N913 in the IGF1R caused predominantly cytoplasmic Compound Library localization of the receptor whereas wild-type IGF1R appeared to localize to the plasma membrane with increased sensitivity to figitumumab. Therefore, NLG at N913 appears to be essential for functional membrane-bound IGF1R and results in an increased response to anti-IGF1R antibody in cancer cells. Figitumumab has been actively tested in patients with multiple myeloma, but the identification of biomarkers and mechanisms is needed to predict treatment responses and thus help with patient selection to maximize clinical benefits. Data from the present study suggest that the level of IGF1R/IR HRs can be a possible diagnostic biomarker for predicting sensitivity to anti- IGF1R antibody, particularly in GC and HCC cells. Previous studies have reported that the level of IGF1R itself may have predictive value in breast, lung, and colorectal cancers . In our study, however, neither expression of IGF1R alone nor levels of other IGF1R associated molecules, including IRS1, could be used to sufficiently predict figitumumab sensitivity . Instead, we found that an important factor for the response to figitumumab seemed to be high expression levels of IR because only drug-sensitive cells showed high levels of IR as well as IGF1R . Considering that several previous studies showed that overexpression of both IGF1R and IR may lead to an increased formation of IGF1R/IR HRs and expand the pool of IGF1 binding sites in FTY720 various human malignancies , we therefore focused on the concept that the level of IGF1R/IR HRs may be an important molecular biomarker for predicting figitumumab sensitivity. Consistent with these earlier reports, we observed that higher IR expression in the cells produced a greater number of endogenous HRs. Furthermore, figitumumab effectively disrupted IGF1-mediated IGF1R/IR HR formation, predominantly in cells overexpressing the HR. We also examined changes of IGF1R/IR HR levels in a mouse HepG2 xenograft model and determined that figitumumab reduced the expression of IGF1R/IR HRs . This observation indicated that anti-IGF1R antibodies may preferentially act against cancer cells overexpressing IGF1R/IR HRs. Although the physiological role of IGF1R/IR HRs is still unclear, a number of previous studies have indicated that they play major roles that may be more important than that of IGF1R . This is because HRs, especially those containing IR-A hemidimers, have a broad binding specificity. IR-A expression upregulates the IGF system by both increasing the affinity of heterodimers for IGFs and allowing insulin to activate the IGF1R in heterodimers .