A nanotherapeutic strategy to target drug‐tolerant cells and overcome EGFR tyrosine kinase inhibitor resistance in lung cancer

For patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC), EGFR tyrosine kinase inhibitors (TKIs) are used as the first-line treatment [1, 2]. Despite initial therapeutic responses, patients invariably experience disease progression due to acquired drug resistance [3]. Resistance arises, in part, because a subset of cancer cells undergoes epithelial-mesenchymal transition (EMT) and remains viable despite exposure to EGFR TKI concentrations that eliminate the bulk population [4]. The surviving cells can be re-sensitized to treatment by prolonged culture in the absence of EGFR TKIs, indicating a transient, potentially reversible, tolerance to these drugs [4]. However, these drug-tolerant cells (DTCs) may regain proliferative potential, evolve, and give rise to diverse stable mechanisms of resistance in patients [5,…