Study identifies mechanism of resistance to targeted therapy in lung cancer patients

Gefitinib acts on the receptor for the epidermal growth factor protein (EGFR) to halt the spread of cancer cells by fitting into the activating pocket of the protein, blocking the growth signals, and thereby depriving the cancer cells of the stimuli they need to survive and proliferate. In 2003, it was approved by the U.S. Food and Drug Administration as a treatment for NSCLC.

Approximately 10 percent of patients experienced complete remission of their disease following clinical trial of the new drug, but later suffered a relapse.

Hypothesizing that the relapses may have been due to another mutation in the EGFR gene which was causing cancer cells to become resistant to the drug, Halmos, together with the study’s corresponding author Daniel Tenen, M.D., a molecular biologist in the Division of Hematology/Oncology at BIDMC, and Susumu Kobayashi, M.D., Ph.D., a physician-scientist in Tenen’s laboratory, analyzed the tumor of a patient whose cancer had recurred after having been treated with gefitinib.

Their studies confirmed the existence of a second mutation that altered gefitinib’s drug-binding pocket so that the gefitinib no longer fit.

Study coauthor Bruce Johnson, M.D., director of the Dana- Farber/Harvard Cancer Center Lung Program, says that researchers are already studying new resistance mechanisms to help develop new inhibitor drugs.