NF-kappaB as a therapeutic target in chronic lymphocytic leukemia.

IMPORTANCE OF THE FIELD: NF-kappaB includes a family of transcription factors that play a critical role in the biology of normal lymphocytes and it is aberrantly activated in chronic lymphocytic leukemia (CLL) cells. Here, we review the role of constitutive NF-kappaB activation in CLL pathogenesis and its potential as a therapeutic target for CLL treatment. AREAS COVERED IN THIS REVIEW: This review highlights the different strategies reported to inhibit NF-kappaB signaling in CLL cells. They include both IkappaB kinase inhibitors and several natural compounds that act at different steps of the pathway. WHAT THE READER WILL GAIN: Targeting NF-kappaB leads to apoptosis of CLL cells, corroborating the role of NF-kappaB in the survival and clonal expansion of these tumoral cells. Moreover, several studies confirmed a synergistic effect between NF-kappaB inhibitors and other antitumoral agents and that inhibition of NF-kappaB could overcome the microenvironmental protection of CLL cells. TAKE HOME MESSAGE: NF-kappaB is a relevant target in CLL and inhibitors of this prosurvival pathway, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients.