CRISPR/Cas-mediated genome editing to treat EGFR-mutant lung cancer: apersonalized molecular surgical therapy

While substantial progress has been made in the treatment of lung cancer with the development of tyrosine kinase inhibitors (TKIs) that target tumor-driving mutations in the epidermal growth factor receptor (EGFR), nearly all patients treated with TKIs ultimately develop drug resistance due to resistance-conferring genomic mutations. CRISPR/Cas9-mediated genome editing is a powerful new technique that allows precise changes to be made to cells' genomes. This technology is currently used widely in research laboratories, but it has yet to make an impact in the clinics. We suggest a potential exciting clinical application for this technical advanceallowing personalized, molecular surgery to correct or destroy the mutated EGFR. After detection of EGFR mutations in individual patients' cancers from biopsy samples, the EGFR-mutant genes will be repaired or destroyed with virus-delivered CRISPR/Cas system. We demonstrate the feasibility of such an approach with examples from the most common primary and secondary EGFR mutations that are encountered. These proposed molecular surgeries on genomic DNA directly target the cause of the disease in a personalized and possibly permanent manner. This approach could be combined with traditional surgery, radiation therapy, or chemo/targeted therapy.