As reported in Clinical Cancer Research, Skinner and colleagues used proteomic profiling to identify PTK2/FAK as a driver of radioresistance in human papillomavirus (HPV)-negative head and neck squamous cell carcinoma.
Using proteomic and transcriptomic analysis of targetable markers, the investigators found that radioresistance was associated with increased expression of numerous targets, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK; also known as PTK2). Inhibition of PTK2/FAK, but not FGFR, resulted in significant radiosensitization, with increased G2/M arrest and potentiated DNA damage. Further, PTK2/FAK overexpression was associated with gene amplification in HPV-negative head and neck squamous cell carcinoma cell lines and clinical tumors.
Assessment in two independent cohorts of patients with locally advanced HPV-negative head and neck squamous cell carcinoma showed that PTK2/FAK amplification was associated with poorer disease-free survival (P = .012 and P = .034); PTK2/FAK mRNA expression was also associated with poorer disease-free survival (P = .03). In addition, PTK2/FAK mRNA (P = .021) and copy number (P = .063) were associated with disease-free survival in the Head and Neck Cancer subset of The Cancer Genome Atlas.
The investigators concluded: “Proteomic analysis identified PTK2/FAK overexpression [as] a biomarker of radioresistance in locally advanced head and neck squamous cell carcinoma, and PTK2/FAK inhibition radiosensitized head and neck squamous cell carcinoma cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative head and neck squamous cell carcinoma.”