Our preclinical study demonstrates that combining PLK1 inhibitors with EGFR/MEK/ERK pathway inhibitors not only exhibits remarkable efficacy in eradicating cancer cells but also effectively overcomes the acquired resistance to EGFR-TKIs, thus offering a potential clinical treatment strategy for EGFR-mutant NSCLC patients. The gene discussed is MAP2K7; the disease is non-small cell lung carcinoma.