Fig. 1.

Cycling persisters upon TKI drug pressure. In unchallenged tumor cells with physiological Nrf2 levels, drug exposure leads to a clonal selection of cells with acquired drug resistance characterized by supraphysiological Nrf2 levels. Only cells with high antioxidant defense levels can proliferation while drug-resistant cells with lower levels do not. Nrf2 and antioxidant defense levels ceased after drug removal, ultimately resembling tumor cells before the initial drug challenge. Hence, drug sensitivity and resistance are dynamic cellular states controlled by a set of antioxidant defense response genes rather than separate entities a priori. Created with BioRender.com