
The study identified GPX4 as a crucial factor promoting the survival of drug-tolerant persister (DTP) cells in ALK+ non-small-cell lung cancer (NSCLC). GPX4 was upregulated in DTP cells, suppressing ROS accumulation. Inhibition of GPX4, combined with ALK-TKI and EGFR/HER3 pathway inhibitors, significantly enhanced ROS levels, suppressed cell growth, and induced cell death. This triple combination therapy offers a promising strategy to overcome ALK-TKI resistance and potentially eradicate tumors in ALK+ NSCLC patients.
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