In a study reported in the Journal of the National Cancer Institute, Eke and colleagues found that simultaneous β1 and epidermal growth factor receptor (EGFR) inhibition resulted in increased cytotoxicity, radiosensitization, and tumor control in human head and neck squamous cell carcinomas.
Compared with β1-integrin inhibition with the monoclonal antibody AIIB2 alone or EGFR inhibition with cetuximab alone, combined targeting resulted in enhanced cytotoxicity and radiosensitization in 8 of 10 human head and neck squamous cell carcinoma cell lines, with response characterized by focal adhesion kinase (FAK) dephosphorylation after β1-integrin inhibition.
In mouse models using two of the cell lines, simultaneous inhibition and radiotherapy resulted in better tumor control in UTSCC15 responder xenografts (hazard ratio [HR] = 6.9, P = .01) vs anti-EGFR monotherapy and radiation, whereas similar activity was not observed in the SAS nonresponder tumor model (HR = 0.9, P = .83). Simultaneous inhibition was found to compromise radiation resistance associated with FAK- and Erk1-mediated prosurvival signals.
The investigators concluded: “Concomitant targeting of β1 integrin and EGFR seems a powerful and promising approach to overcome radioresistance of head and neck squamous cell carcinomas.” ■