Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Br J Haematol. 2010 Oct;151(1):3-15. doi: 10.1111/j.1365-2141.2010.08262.x. Epub 2010 Jul 7.
In the last decade, the novel agents lenalidomide, bortezomib, and thalidomide have dramatically improved outcomes for patients with multiple myeloma (MM). A number of new therapies with precise targets involved in MM cell growth and replication are now in development and have the potential for further improvements. Second-generation proteasome inhibitors and thalidomide derivatives may offer increased efficacy and safety. Investigational therapies with rationally selected targets in MM include inhibitors of histone deacetylase, heat shock protein 90, mammalian target of rapamycin, BCL2, Akt, mitogen-activated protein kinase, and telomerase. In addition, monoclonal antibodies directed against several targets have been developed and many are showing promise in initial clinical trials in MM. Interest in the ancient remedy of arsenic trioxide has been revived because of its proapoptotic effects on mitochondria, despite its established toxicities. In general, combination regimens are proving the most efficacious, which is to be expected given the multiple overlapping pathways responsible for MM growth and progression.
在过去的十年中，新型药物来那度胺、硼替佐米和沙利度胺极大地改善了多发性骨髓瘤（MM）患者的预后。目前有许多针对 MM 细胞生长和复制中涉及的精确靶点的新疗法正在开发中，并有进一步改善的潜力。第二代蛋白酶体抑制剂和沙利度胺衍生物可能具有更高的疗效和安全性。在 MM 中具有合理选择靶点的研究性治疗包括组蛋白去乙酰化酶抑制剂、热休克蛋白 90、哺乳动物雷帕霉素靶蛋白、BCL2、Akt、丝裂原活化蛋白激酶和端粒酶抑制剂。此外，已经开发出针对多个靶点的单克隆抗体，并且许多抗体在 MM 的初始临床试验中显示出前景。尽管三氧化二砷具有既定的毒性，但由于其对线粒体的促凋亡作用，人们对这种古老疗法的兴趣重新燃起。一般来说，联合治疗方案被证明是最有效的，这是因为有许多重叠的途径负责 MM 的生长和进展。
