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

Derangement of the nuclear factor κB (NF‐κB) 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‐κB 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‐κB, which can be exploited therapeutically. Since each subtype of lymphoid cancer utilizes different mechanisms to activate NF‐κB, several different therapeutic strategies are needed to address this pathogenetic heterogeneity. Fortunately, a number of drugs that block signaling cascades leading to NF‐κB are in early phase clinical trials, several of which are already showing activity in lymphoid malignancies.