To evaluate whether PTPRT promoter methylation may serve as a predictive biomarker for STAT3 targeted therapies, we first determined EC50 values for selective STAT3 inhibitors in a panel of 8 HNSCC cell lines (Figures 6A and 6B) that exhibit varying levels of PTPRT promoter methylation as determined by MSP (summarized in Figures 6C and 6D). Figures 6E and 6F illustrate that PTPRT promoter methylation and sensitivity to Stattic (a STAT3 SH2 domain inhibitor) or JSI-124 (a JAK/STAT3 pathway inhibitor) are significantly correlated (P < 0.05), indicating that HNSCC tumors that exhibit PTPRT promoter hypermethylation may be most sensitive to treatment with STAT3 inhibitors.