Sloan-Kettering Institute for Cancer Research
Overcoming Resistance to Newest EGFR-Inhibiting Lung Cancer Drugs
Epidermal growth factor receptor (EGFR) is a cell surface protein that promotes cell growth once controlled by epidermal growth factor. Some lung cancers have mutations in EGFR, resulting in hyperactivation of the receptor and uncontrolled proliferation of cancer cells. Most patients with EGFR mutant lung cancer initially respond to drugs that inhibit EGFR but eventually develop resistance. We will develop combination therapy to prevent and/or overcome resistance to the newest EGFR inhibitors by triggering a regulated form of cell death known as apoptosis in cancer cells. We will also investigate the mechanisms underlying resistance to the newest EGFR inhibitors.
Update: We have performed screening of a custom chemical library to identify agents that enhance apoptosis of an EGFR inhibitor called AZD9291. We have discovered molecules that work with AZD9291 to induce cell death in EGFR mutant lung cancer. We are also studying a combination strategy that may be able to overcome acquired resistance to AZD9291 and another EGFR inhibitor.