Synergistic apoptosis in head and neck squamous cell carcinoma cells by co-inhibition of insulin-like growth factor-1 receptor signaling and compensatory signaling pathways.

Axelrod MJ, Mendez RE, Khalil A, Leimgruber SS, Sharlow ER, Capaldo B, Conaway M, Gioeli DG, Weber MJ, Jameson MJ

Background: In head and neck squamous cell carcinoma (HNSCC), resistance to single agent targeted therapy may be overcome by co-targeting of compensatory signaling pathways. Methods: A targeted drug screen with 120 combinations was used on 9 HNSCC cell lines. Results: Multiple novel drug combinations demonstrated synergistic growth inhibition. Combining the insulin-like growth factor-1 receptor (IGF1R) inhibitor BMS754807 with either the HER-family inhibitor BMS599626 or the Src-family kinase inhibitor dasatinib resulted in substantial synergy and growth inhibition. Depending on the cell line, these combinations induced synergistic or additive apoptosis; when synergistic apoptosis was observed, AKT phosphorylation was inhibited to a greater extent than either drug alone. Conversely, when additive apoptosis occurred, AKT phosphorylation was not reduced by the drug combination. Conclusions: Combined IGF1R/HER family and IGF1R/Src family inhibition may have therapeutic potential in HNSCC. AKT may be a node of convergence between IGF1R signaling and pathways that compensate for IGF1R inhibition. Head Neck, 2014.

Cell Lysis
Western Blot

Share this article

July, 2014



 See all events

Twitter feed


 See all news