Proteomic Profiling Identifies PTK2/FAK as a Driver of Radioresistance in HPV-negative Head and Neck Cancer
作者： Heath D Skinner , Uma Giri , Liang Yang , Sang Hyeok Woo , Michael D Story
DOI: 10.1158/1078-0432.CCR-15-2785
关键词:
摘要: Purpose: Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, local failure after treatment remains the major cause of disease-related mortality. To date human papillomavirus (HPV) only known clinically validated, targetable biomarkers response to radiation in HNSCC. Experimental Design: We performed proteomic transcriptomic analysis radioresistance HPV-negative HNSCC lines vitro, tested whether pharmacologic blockade candidate sensitized cells radiotherapy. Candidate were then investigated several independent cohorts patients Results: Increased expression targets was associated radioresistance, including FGFR, ERK1, EGFR, focal adhesion kinase (FAK), also as PTK2. Chemical inhibition PTK2/FAK, but not led significant radiosensitization increased G2/M arrest potentiated DNA damage. PTK2/FAK overexpression gene amplification clinical tumors. In two locally advanced HNSCC, highly poorer disease-free survival (DFS) (P=0.012 P=0.034). mRNA worse DFS (P=0.03). Moreover, both (P=0.021) copy number (P=0.063) Neck Cancer subgroup The Genome Atlas. Conclusion: Proteomic identified a biomarker radiosensitized cells. Combinations radiotherapy merit further evaluation therapeutic strategy for improving control
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