TY - JOUR
T1 - Can NF-κB be a target for novel and efficient anti-cancer agents?
AU - Olivier, Sabine
AU - Robe, Pierre
AU - Bours, Vincent
PY - 2006/10/30
Y1 - 2006/10/30
N2 - Since the discovery of the NF-κB transcription factor in 1986 and the cloning of the genes coding for NF-κB and IκB proteins, many studies demonstrated that this transcription factor can, in most cases, protect transformed cells from apoptosis and therefore participate in the onset or progression of many human cancers. Molecular studies demonstrated that ancient widely used drugs, known for their chemopreventive or therapeutic activities against human cancers, inhibit NF-κB, usually among other biological effects. It is therefore considered that the anti-cancer activities of NSAIDs (non-steroidal anti-inflammatory drugs) or glucocorticoids are probably partially related to the inhibition of NF-κB and new clinical trials are being initiated with old compounds such as sulfasalazine. In parallel, many companies have developed novel agents acting on the NF-κB pathway: some of these agents are supposed to be NF-κB specific (i.e. IKK inhibitors) while others have wide-range biological activities (i.e. proteasome inhibitors). Today, the most significant clinical data have been obtained with bortezomib, a proteasome inhibitor, for the treatment of multiple myeloma. This review discusses the preclinical and clinical data obtained with these various drugs and their putative future developments.
AB - Since the discovery of the NF-κB transcription factor in 1986 and the cloning of the genes coding for NF-κB and IκB proteins, many studies demonstrated that this transcription factor can, in most cases, protect transformed cells from apoptosis and therefore participate in the onset or progression of many human cancers. Molecular studies demonstrated that ancient widely used drugs, known for their chemopreventive or therapeutic activities against human cancers, inhibit NF-κB, usually among other biological effects. It is therefore considered that the anti-cancer activities of NSAIDs (non-steroidal anti-inflammatory drugs) or glucocorticoids are probably partially related to the inhibition of NF-κB and new clinical trials are being initiated with old compounds such as sulfasalazine. In parallel, many companies have developed novel agents acting on the NF-κB pathway: some of these agents are supposed to be NF-κB specific (i.e. IKK inhibitors) while others have wide-range biological activities (i.e. proteasome inhibitors). Today, the most significant clinical data have been obtained with bortezomib, a proteasome inhibitor, for the treatment of multiple myeloma. This review discusses the preclinical and clinical data obtained with these various drugs and their putative future developments.
KW - Apoptosis
KW - Cancer
KW - Chemotherapy
KW - IKK
KW - NF-κB
KW - Proteasome
UR - http://www.scopus.com/inward/record.url?scp=33749051213&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2006.07.023
DO - 10.1016/j.bcp.2006.07.023
M3 - Review article
C2 - 16973133
AN - SCOPUS:33749051213
SN - 0006-2952
VL - 72
SP - 1054
EP - 1068
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 9 SPEC. ISS.
ER -