Mechanistically, CP was found to prevent NRF2 nuclear accumulation and promote its degradation through the β-TrCP-dependent pathway, leading to ROS accumulation and marked suppression of anchorage-independent growth in several NSCLC cell lines with mutant KEAP1. Moreover, when used alone or in combination with Rapamycin in vitro or in vivo, CP impaired the growth of tumors harboring KEAP1 or both KEAP1/LKB1 mutations, a frequent event in lung cancer. The gene discussed is NFE2L2; the disease is non-small cell lung carcinoma.