Health Research Incorporated, Roswell Park Cancer Institute Division
Reversing Drug Resistance in EGFR Mutant Lung Cancers
EGFR mutant lung cancers are diagnosed in nearly 250,000 individuals worldwide each year. These cancers are treated using drugs called EGFR tyrosine kinase inhibitors (EGFR TKIs). Although initially effective, almost all tumors stop responding to treatment in 1.5 years. In an increasing number of cases, EGFR TKIs stop working because tumors undergo a process termed the epithelial-mesenchymal transition (EMT). Our studies test a novel approach to reverse EMT and restore tumor sensitivity to EGFR TKIs. Our approach uses a protective shell or nanoparticle (NP) to deliver vitamin D (VD) and a drug called CTA091 to EGFR mutant tumors. Once inside tumor cells, VD reverses EMT. CTA091 prevents tumors from destroying VD, thus sustaining therapeutic benefit. The proposed studies will establish the safety and activity of our NP in combination with EGFR TKIs in lung tumor models, including patient avatars. Positive results will provide a solution to the problem of EMT-mediated drug resistance.