NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms

The NF-kappa B pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-kappa B pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti-apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-kappa B pathway has emerged as a target for therapy. In the review, we present the physiologic role of the NF-kappa B pathway and recent advances in better understanding of the pathologic roles of the NF-kappa B pathway in major types of lymphoid neoplasms. We also provide an update of clinical trials that use NF-kappa B pathway inhibitors. These trials are exploring the clinical efficiency of combining NF-kappa B pathway inhibitors with various agents that target diverse mechanisms of action with the goal being to optimize novel therapeutic opportunities for targeting oncogenic pathways to eradicate cancer cells. (C) 2016 Elsevier Ltd. All rights reserved.