fig1

Figure 1. Development of different generations of EGFR-mut TKIs in NSCLC. EGFR-dependent resistance mechanisms are associated with different EGFR mutations (e.g., del19, L858R, T790M, C797S, and others). Currently approved TKIs are also listed. Fourth-generation TKIs targeting C797S are currently under clinical development. The bottom half of the illustration depicts EGFR-independent resistance mechanisms. ??: 5th-generation TKIs are currently unknown (no data in the literature so far). This figure was created using BioRender.com (modified after^[1,10-12]) (https://biorender.com/o0zo69u). EGFR: Epidermal growth factor receptor; TKIs: tyrosine kinase inhibitors; NSCLC: non-small cell lung cancer; EMT: epithelial-mesenchymal transition; ASCL1: achaete-scute homolog 1; MUC1-C: Mucin-1-C; ecDNA: extrachromosomal DNA; DTP: drug-tolerant persister cell; AXL: AXL receptor tyrosine kinase; MET: mesenchymal-epithelial transition factor; TROP2: trophoblast cell-surface antigen 2; HER2/3: human epidermal growth factor receptor 2/3; RET: rearranged during transfection; ALK: anaplastic lymphoma kinase; FGFR: fibroblast growth factor receptor; NTRK: neurotrophic receptor tyrosine kinase; BRAF: B-Raf proto-oncogene, serine/threonine kinase; PIK3CA: phosphoinositide-3-kinase.