Potential CRISPR/Cas9 Gene Editing Applications in Reversing Acquired Resistance to EGFR-TKIs due to Secondary and Tertiary Mutations to EGFR in NSCLC

Lung cancer treatment has long been a major field of study in research due to the com-plexity and variability of cancer. Because drug resistance is a major hurdle for lung cancer treat-ment, in this article, we will review the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) used for the treatment of Non Small Cell Lung Cancer (NSCLC) and the EGFR mutations that cause resistance to them. Then, we will discuss the applications of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) genome ed-iting in medical treatment. The proposed treatment is specifically for NSCLC patients who have acquired resistance to EGFR TKIs due to mutations to EGFR such as T790M and C797S and would make these TKIs become effective once again. Currently, there is no treatment targeting C797S on the market, but fourth-generation EGFR-TKIs are currently in trial [1,2]. (Figure 1) This proposal will review the potential steps and options available as well as some challenges that may complicate the process.