Proteomic Profiling Identifies Ptk2/Fak As A Targetable Marker Of Radioresistance In Head And Neck Cancer

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAOne of the primary treatments for head and neck squamous cell carcinoma (HNSCC) is radiotherapy. Despite decades of study, few if any targetable biomarkers for resistance to this modality. To systematically evaluate resistance to radiotherapy in HNSCC, we evaluated 50 HNSCC cell lines using reverse phase protein array (RPPA). Utilizing this method we identified 11 protein markers with altered expression in radioresistant HNSCC cell lines (FDR 1%), including PTK2/FAK. Both PTK2/Fak gene expression and copy number were highly correlated to PTK2/Fak protein expression and both were associated with radioresistance in these cell lines. Additionally, in clinical samples from the TCGA, PTK2/Fak copy number was highly associated with gene expression, with high expression levels in HNSCC tumors. To validate the association between PTK2/Fak and clinical radioresistance in HNSCC, we examined PTK2/FAK copy number in two separate cohorts of HNSCC patients treated uniformly with radiotherapy (n = 39 and n = 44). In both cohorts, PTK2/Fak amplification was associated with treatment failure following radiotherapy (p = 0.04 and p = 0.03 respectively and p = 0.004 for the combined population). Additionally, in a separate cohort of HNSCC patients treated with radiotherapy, high levels of PTK2/Fak gene expression were associated with failure following radiotherapy (p = 0.02). Additionally, in vitro pharmacologic inhibition of PTK2/FAK function led to radiosensitization in multiple HNSCC cell lines, primarily via induction of G2/M arrest, with minimal apoptosis observed. Taken together, these data identify a validated, targetable biomarker of radioresistance in HNSCC.Citation Format: Heath D. Skinner, Uma Giri, John S. Yordy, Michael D. Story, Jing Wang, Lauren A. Byers, Michelle D. Williams, Adel K. El-Naggar, Sang H. Woo, Liang P. Yang, You Fan, Curtis R. Pickering, Jeffrey N. Myers,, John V. Heymach. Proteomic profiling identifies PTK2/FAK as a targetable marker of radioresistance in head and neck cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3441. doi:10.1158/1538-7445.AM2015-3441