Lung cancer is the leading cause of cancer mortality worldwide and lung adenocarcinoma is the most common type. Many cases of lung adenocarcinoma are attributed to a mutation in a gene for the epidermal growth factor receptor (EGFR). Lung cancer with changes in EGFR is initially treatable with a family of chemotherapeutic agents called tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. However, patients often develop resistance to these drugs through the acquisition of additional changes or secondary mutations that allow cancer cells to evade treatment.
Some secondary mutations to the EGFR gene that allow lung cancer cells to survive in the presence of current chemotherapy are known. These secondary changes are now the focus of targeted efforts to create drugs to specifically interfere with the mutated form of the protein. Unfortunately, in 40% of the cases in which patients become resistant to therapy, the molecular events that confer this resistance are not known. Without knowing the changes that sustain the survival of these cells it remains impossible to specifically and effectively target them with anti-cancer drugs.