Olivier Sabine, Robe Pierre, Bours Vincent
Department of Rheumatology, Centre for Biomedical Integrative Genoproteomics, University of Liège, CHU B35, Sart-Tilman, 4000 Liège, Belgium.
Biochem Pharmacol. 2006 Oct 30;72(9):1054-68. doi: 10.1016/j.bcp.2006.07.023. Epub 2006 Sep 14.
Since the discovery of the NF-kappaB transcription factor in 1986 and the cloning of the genes coding for NF-kappaB and IkappaB 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-kappaB, 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-kappaB 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-kappaB pathway: some of these agents are supposed to be NF-kappaB 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.
自1986年发现核因子-κB转录因子以及编码核因子-κB和IκB蛋白的基因被克隆以来，许多研究表明，在大多数情况下，这种转录因子能够保护转化细胞免于凋亡，因此参与多种人类癌症的发生或发展。分子研究表明，一些长期广泛使用的、以对人类癌症具有化学预防或治疗活性而闻名的药物，通常在产生其他生物学效应的同时还能抑制核因子-κB。因此，人们认为非甾体抗炎药（NSAIDs）或糖皮质激素的抗癌活性可能部分与抑制核因子-κB有关，并且正在针对柳氮磺胺吡啶等旧化合物开展新的临床试验。与此同时，许多公司已研发出作用于核因子-κB信号通路的新型药物：其中一些药物被认为对核因子-κB具有特异性（即IKK抑制剂），而其他药物则具有广泛的生物学活性（即蛋白酶体抑制剂）。如今，蛋白酶体抑制剂硼替佐米在治疗多发性骨髓瘤方面已获得最为显著的临床数据。本综述讨论了使用这些不同药物所获得的临床前和临床数据以及它们可能的未来发展。
