Overcoming Resistance to EGFR Inhibitors in EGFR-Mutant NSCLC

Dr. Faber’s research program includes studying resistance mechanisms to targeted therapies in lung cancer. During his postdoctoral training, he discovered that low expression levels of functional BIM, a pro-apoptotic protein, was sufficient to impart resistance to EGFR inhibitors in EGFR mutant lung cancer through loss of a cell death response. Loss of functional BIM is now part of clinical decision making for EGFR mutant lung cancer patients and combination therapy of EGFR inhibitors with BH3 mimetics to rescue or improve cell death responses are being explored clinically. Dr. Faber’s laboratory more recently linked epithelial-to-mesenchymal related EGFR inhibitor resistance with low levels of BIM, and a deficient cell death response.

• 1. The EGFR in NSCLC: Biology, activation and targeting2. Background of the EGFR receptor, biology of activation, regulation of EGFR in normal cells and cancer cells, mutations as oncogenic in NSCLC3. Background of EGFR inhibitor development and implementation, assessment of how EGFR inhibitors have been implemented and are currently implemented4. YAP signalling in EGFR inhibitor resistance5. Apoptosis resistance in EGFR inhibitor resistance6. EGFR mutations and resistance to EGFR inhibitors7. SCLC transformation and resistance to EGFR inhibitors8. EMT and resistance to EGFR inhibitors in EGFR mutant NSCLC9. Intratumoral heterogeneity and resistance10. Clinical trials of EGFR inhibitors in EGFR mutant lung cancer11. Methodology of the detection of resistant mechanisms in the lung cancer clinic