Johns Hopkins University
Targeting a Gene Involved in Lung Cancer Drug Resistance
Many lung cancers are caused by cell mutations that make them highly responsive to targeted treatments, such as the EGFR inhibitor erlotinib. Lung cancers with EGFR mutations initially respond very well to erlotinib but all patients eventually develop resistance. One way resistance develops is through a change called epithelial/mesenchymal transition (EMT). A gene called Twist1 is one of the key regulators of EMT. Our previous work suggests Twist1 is overly active in many lung tumors and plays a role in development of the cancer. We will study the role of Twist1 in erlotinib resistance in EGFR mutant lung cancers. The findings could lead to therapy that reverses Twist1-induced erlotinib resistance.
Update: Part of our research has involved determining whether Twist1 may regulate the NOX4 gene and whether inhibiting NOX4 could reverse Twist1?induced drug resistant lung tumors. We have preliminary data that showed a significant difference in treatment response when a NOX4 inhibitor is used in combination with the lung cancer drug erlotinib as compared to erlotinib alone, in a genetically engineered lung cancer model specifically designed to be resistant to erlotinib.