[NF-kappaB: an essential signaling pathway, track for new treatments]

NF-kB is an ubiquitous transcription factor involved in many biological activities such as the control of innate and adaptive immunity, inflammatory reaction and the control of apoptosis. In most cell types, NF-kB is inactivated through its binding to an inhibitor, Ikbeta, and NF-kB activation requires Ikbeta phosphorylation and subsequent proteasome-mediated degradation. In cancer cells, NF-kB can be constitutively active and can also be activated in response to chemotherapeutic agents or ionizing radiations. In both cases, the NF-kB activity in cancer cells inhibits apoptosis and thus limits the cytotoxicity of the treatments. Recently, NF-kB inhibitors have been developed and their anti-tumoral activity has been evaluated in various models. A proteasome inhibitor, bortezomib, is highly active in refractory multiple myeloma, a cancer with a high constitutive NF-kB activity. The same compound is also tested for the treatment of many human cancers, either as a single agent or in combination with conventional treatments.