Low Expression of the E3 Ubiquitin Ligase CBL Confers Chemoresistance in Human Pancreatic Cancer and Is Targeted by Epidermal Growth Factor Receptor Inhibition

Abstract

Low CBL causes chemoresistance in PDAC via stress-induced EGFR activation that can be effectively abrogated by EGFR inhibition. These results suggest that dysregulation of ubiquitination is a key mechanism of EGFR hyperactivation in PDAC and that low CBL may define PDAC tumors likely to respond to erlotinib treatment.