EGFR and cancer: Our results on ZNF216 functions could have both basic as well as significant clinical relevance: (a) this molecular regulator may be critical in tumor cell-specific EGFR overexpression, a common occurrence in a variety of epithelial tumors; and (b) ZNF216 could be a novel therapeutic target, up-regulation of which could contribute to the degradation of EGFR protein leading to reduced clonogenic survival of EGFR-addicted cancer cells.