IGF-2/IGF-1R Inhibition Shows Promise in Esophageal Cancer

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In a study reported in Clinical Cancer Research, Li and colleagues found that overexpression of Id1 protein resulted in insulin-like growth factor (IGF)-2 production, which, in turn, resulted in esophageal cancer cell proliferation, survival, and invasion via autocrine activation of AKT.

Overexpression of IGF-2 was identified in 60% of tumor samples from patients with esophageal cancer and was associated with upregulation of Id1 and phosphorylated AKT. In Id1-overexpressing xenografts, secreted IGF-2 promoted growth of distant esophageal tumors and metastasis of circulating cancer cells.

Intratumoral injection of IGF-2 antibody and intraperitoneal injection of the IGF-1 receptor (IGF-1R) antibody cixutumumab resulted in significant suppression of tumor growth and metastasis in mice. Further, cixutumumab increased the sensitivity of tumor xenografts to fluorouracil and cisplatin.

The investigators concluded, “The Id1–[IGF-2–IGF-1R]–AKT signaling cascade plays an important role in esophageal cancer progression. Blockade of [IGF-2/IGF1R] signaling has therapeutic potential in the management of esophageal cancer.” ■

Li B, et al: Clin Cancer Res 20:2651-2662, 2014.