title: Targeting nuclear factor-kappa B to overcome resistance to chemotherapy.
abstract: 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-κB pathway. NF-κB 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, NF-κB has emerged as a promising anti-cancer target. Here, we describe the role of NF-κB in cancer and in the development of resistance, particularly cisplatin. Additionally, the potential benefits and disadvantages of targeting NF-κB signaling by pharmacological intervention will be addressed.
authors.affiliation: Department of Clinical Medicine, Thoracic Oncology Research Group, Trinity College Dublin, St. James's Hospital Ireland Dublin, Ireland.
authors.forename: P
authors.initials: P
authors.lastname: Godwin
authors.forename: A M
authors.initials: AM
authors.lastname: Baird
authors.forename: S
authors.initials: S
authors.lastname: Heavey
authors.forename: M P
authors.initials: MP
authors.lastname: Barr
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Byrne
authors.forename: K
authors.initials: K
authors.lastname: Gately
keywords: NF-κB; apoptosis; cancer; chemotherapy; cisplatin; oncogene; resistance