The combination of pan-ErbB tyrosine kinase inhibitor CI-1033 and lovastatin: A potential novel therapeutic approach in squamous cell carcinoma of the head and neck

• Main Author: Guimond, Tanya
• Language: en
• Published: 2011
• Subjects: EGFR; ErbB Receptors; CI-1033; Mevalonate; Cancer; Tyrosine Kinase Inhibitor; Lovastatin; Squamous Cell Carcinoma
• Online Access: http://hdl.handle.net/10393/20267

The ErbB family of receptors are key regulators of growth, differentiation, migration and survival of epithelial cells. CI-1033 is an irreversible pan-ErbB tyrosine kinase inhibitor that has the ability to inhibit EGFR function but has shown limited therapeutic efficacy. Lovastatin targets the activity of HMG-CoA reductase, the rate-limiting step in the mevalonate pathway. In this study, the ability of lovastatin to potentiate the cytotoxic effects of CI-1033 was evaluated. The combination of lovastatin and CI-1033 exhibited some cooperative cytotoxic activity in a squamous cell carcinoma–derived cell line. This combination resulted in enhanced cell death by induction of a potent apoptotic response. Furthermore, this drug combination inhibited EGF-induced EGFR autophosphorylation and activation of the downstream signaling effectors, ERK and AKT. These findings suggest that combining lovastatin and tyrosine kinase inhibitors may represent a novel combinational therapeutic approach in squamous cell carcinoma of the head and neck.