Pathogenetic importance and therapeutic implications of NF-κB in lymphoid malignancies

Derangement of the nuclear factor ?B (NF-?B) pathway initiates and/or sustains many types of human cancer. B-cell malignancies are particularly affected by oncogenic mutations, translocations, and copy number alterations affecting key components the NF-?B pathway, most likely owing to the pervasive role of this pathway in normal B cells. These genetic aberrations cause tumors to be addicted to NF-?B, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF-?B, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF-?B are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies.