Targeting nuclear factor-kappa B to overcome resistance to chemotherapy

Intrinsic or acquired resistance to chemotherapeutic agents is a common phenomenon and a major challenge in the treatment of cancer patients. Chemoresistance is defined by a complex network of factors including multi-drug resistance proteins, reduced cellular uptake of the drug, enhanced DNA repair, intracellular drug inactivation, and evasion of apoptosis. Pre-clinical models have demonstrated that many chemotherapy drugs, such as platinum-based agents, antracyclines, and taxanes, promote the activation of the NF-kappa B pathway. NE-kappa B is a key transcription factor, playing a role in the development and progression of cancer and chemoresistance through the activation of a multitude of mediators including anti-apoptotic genes. Consequently, NE-kappa B has emerged as a promising anti-cancer target. Here, we describe the role of NE-kappa B in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NE-kappa B signaling by pharmacological intervention will be addressed.