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It is the expected effect of proteasome inhibition. Resistant cells develop mechanisms that decrease the endoplasmic reticulum stress. This review covers current efforts to understand the nature of this adaptation. It focuses on druggable targets that can potentially enhance proteasome inhibitors activity or resensitize resistant patients to this type of therapy.In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (