11– 13 Among patients with wild-type KRAS CRC, the single-agent response rate is modest (17% v 0% in unselected patients) with panitumumab monotherapy, 14 and it is 13% with cetuximab monotherapy. 10 Cetuximab had a 17% to 23% response rate when combined with irinotecan in patients whose tumors had progressed during patient treatment with irinotecan and an approximate 9% to 11% single-agent response rate. 7– 9Ĭetuximab is a human-murine monoclonal antibody that targets the EGFR. 4 IGF-1R mediated signaling may also mediate resistance to epidermal growth factor receptor (EGFR) inhibition, and combined IGF-1R and EGFR inhibition has resulted in enhanced growth inhibition in selected preclinical models. 5– 6 Preclinical studies demonstrate that IGF is a strong mitogen in colorectal cancer (CRC). IMC-A12 is a recombinant fully human immunoglobulin G1 monoclonal antibody that specifically targets the human IGF-1R. 2 A large number of preclinical and clinical studies have implicated the IGF-1R and its ligands, IGF-1 and IGF-2, in the development and progression of cancer. 2 The principal pathways for transduction of the IGF signal are the mitogen-activated protein kinase and phosphatidylinositol 3-kinase (PI3K)/Akt pathways. 1 IGF-1R is activated by two high affinity binding ligands, insulin-like growth factor (IGF) 1 and IGF-2. The type 1 insulin-like growth factor receptor (IGF-1R) is a member of a family of transmembrane tyrosine kinases that includes the insulin receptor and the insulin receptor–related receptor.
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