Previously, Wael El-Rifai, M.D., Ph.D., and colleagues found that DARPP-32, a protein abundant in neurons and most commonly associated with addiction, is overexpressed in two-thirds of all gastric cancers. The protein is also overexpressed in several other cancer types and appears to inhibit gastric cancer cells’ ability to commit “suicide” (apoptosis).
The researchers have now investigated the involvement of DARPP-32 expression in the resistance of gastric cancer cells to gefitinib (Iressa). They report in the journal Gastroenterology that DARPP-32 enhances survival of cultured gastric cancer cells and increases resistance to gefitinib by promoting activity of the epidermal growth factor receptor (EGFR) pathway. In mice, reducing DARPP-32 in gastric cancer cells led to smaller tumors with increased response to gefitinib. The results suggest that therapies that reduce DARPP-32 activity may be helpful in preventing resistance to this important targeted therapy.