Our specific objective was to develop patient‐derived xenograft (PDX) models for studies of HNSCC gene transfer, including experiments to evaluate: (1) malignant cell killing by purine base compounds (6‐methylpurine [MeP], F‐Ade), (2) transduction with recombinant adenovirus encoding E. coli PNP, (3) in vivo anticancer activity, (4) protein receptors available in situ for nucleotide delivery to PDX tumors, and (5) viral fiber modification for enhanced transduction efficiency. Here, PNP is linked to head and neck squamous cell carcinoma.