Defining the Sensitivity Landscape of EGFR Variants to Tyrosine Kinase Inhibitors

Tyrosine kinase inhibitor (TKI) is a standard treatment for patients with NSCLC harboring constitutively active epidermal growth factor receptor (EGFR) mutations. However, most rare EGFR mutations lack treatment regimens except for the well-studied ones. We constructed two EGFR variant libraries containing substitutions, deletions, or insertions using the saturation mutagenesis method. All the variants were located in the EGFR mutation hotspot (exons 18-21). The sensitivity of these variants to afatinib, erlotinib, gefitinib, icotinib, and osimertinib was systematically studied by determining their enrichment in massively parallel cytotoxicity assays using an endogenous EGFR-depleted cell line.

Source: Translational Research - November 5, 2022 Category: Research Authors: LEI AN, YUEQIANG WANG, GUANGYAO WU, ZHENXING WANG, ZEYUAN SHI, CHANG LIU, CHUNLI WANG, MING YI, CHENGUANG NIU, SHAOFENG DUAN, XIAODONG LI, WENXUE TANG, KONGMING WU, SHUQING CHEN, HONGEN XU Source Type: research