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Despite the advances made in cancer treatment in the past decades, therapeutic efficacy is still quite challenging, partially due to the emergence of multidrug resistance (MDR). It is crucial to decipher the underlying mechanisms of resistance in order to develop new therapeutic strategies for cancer patients. Previous studies have shown that activation of nuclear factor-κB (NF-κB) plays key roles in various cellular processes including proliferation, anti-apoptosis, metastasis, invasion, and chemoresistance. In this review, we conduct an integrated analysis of the evidence suggesting the vital roles of the NF-κB signaling pathway in MDR during chemotherapy, immunotherapy, endocrine, and targeted therapy. A literature search was performed on NF-κB and drug resistance in PubMed up to February 2023. This review summarizes that the NF‐κB signaling pathway exhibits a crucial role in enhancing drug resistance in chemotherapy, immunotherapy, endocrine, and targeted therapy. The application of combination therapy with existing antineoplastic drugs and a safe NF-κB inhibitor could become a promising strategy in cancer treatment. A better understanding of the pathway and mechanisms of drug resistance may help exploit safer and more effective NF-κB-targeting agents for clinical use in the future.

Modulating multidrug resistance to drug-based antitumor therapies through NF-κB signaling pathway: mechanisms and perspectives