Correlation between Gene Expression of IGF-1R Pathway Markers and Cetuximab Benefit in Metastatic Colorectal Cancer

作者：Fei Huang, Lian Xu, Shirin Khambata‐Ford · 发表于：Clinical Cancer Research · 年份：2012 · DOI：10.1158/1078-0432.ccr-11-1135 · 被引用次数：35 · 研究领域：Colorectal Cancer Treatments and Studies、Growth Hormone and Insulin-like Growth Factors、HER2/EGFR in Cancer Research

PURPOSE: This study examined potential correlations between markers related to the insulin-like growth factor-1 receptor (IGF-1R) pathway and clinical benefit from the anti-epidermal growth factor receptor (EGFR) monoclonal antibody cetuximab in metastatic colorectal cancer (mCRC). EXPERIMENTAL DESIGN: Gene expression profiles for 70 pretreatment specimens from metastatic lesions of patients with chemorefractory mCRC receiving cetuximab monotherapy were analyzed using 74 predefined Gene-Chip probesets representing 33 unique IGF-1R pathway markers to determine correlations with progression-free survival (PFS) and disease control rate. RESULTS: Higher IGF-1R, higher GRB(7), and lower INSIG(2) expression were associated with longer PFS with cetuximab in univariate analyses, particularly in patients with wild-type K-Ras tumors: median, 122 versus 60 days (P = 0.01), 122 versus 57 days (P = 0.011), and 57 versus 156 days (P < 0.0001), favoring higher IGF-1R, higher GRB(7), and lower INSIG(2) expression, respectively. Lower IGF-1 expression was associated with a PFS benefit with cetuximab, whereas lower IGFBP(3) and INSR expression levels showed trends for a PFS benefit. Lower INSIG(2) expression (vs. higher expression) was associated with greater PFS in the high epiregulin-expressing group (P = 0.001), but not in the low-expressing cohort suggesting an effect independent from the previously reported effect of epiregulin expression. Lower INSIG(2) expression was also associated wit...