Treatment with tyrosine kinase inhibitors (TKIs) is the standard of care for lung cancer patients positive for mutations in the EGFR gene. Unfortunately, within a year or so, a vast majority of patients develop resistance against TKIs treatment. Although numerous mechanisms of resistance have been described, in about 30% of cases the mechanism of resistance remains unknown. In this project, we propose to identify genetic alterations contributing to the EGFR TKI resistance by characterizing the genome of TKI-sensitive and TKI-resistant tumor from the same patient. I anticipate this study to have significant impact on the management of lung cancer and help in better selection of patients for the treatment.
Figure: The schema for identification of novel resistance mechanisms using primary tumors from EGFR mutated non-small cell lung cancer patients