xCT Inhibition Depletes CD44v-Expressing Tumor Cells That Are Resistant to EGFR-Targeted Therapy in Head and Neck Squamous Cell Carcinoma

摘要: The targeting of antioxidant systems that allow stem-like cancer cells to avoid the adverse consequences oxidative stress might be expected improve efficacy treatment. Here, we show head and neck squamous cell carcinoma (HNSCC) express variant isoforms CD44 (CD44v) rely on activity cystine transporter subunit xCT for control their redox status. inhibition selectively induces apoptosis in CD44v-expressing tumor without affecting CD44v-negative differentiated same tumor. In contrast undifferentiated cells, manifest EGF receptor (EGFR) activation EGFR survival. Combined treatment with inhibitors xCT-dependent transport resulted a synergistic reduction EGFR-expressing HNSCC growth. Thus, xCT-targeted therapy may deplete concurrently sensitize remaining differentiating available treatments including EGFR-targeted therapy.