Grant Steven
Virginia Commonwealth University/Massey Cancer Center, 401 College Street, PO Box 980035, Richmond, VA 23298-0035, USA.
Best Pract Res Clin Haematol. 2008 Dec;21(4):629-37. doi: 10.1016/j.beha.2008.08.003.
The concept of combining targeted agents for the treatment of acute myeloid leukemia (AML) is a relatively new but potentially promising area of investigation. A number of targeted agents may have limited single-agent activity but could show significant promise when used in conjunction with other types of similar compounds. Combinations of targeted agents may effectively interrupt multiple pathways in either a linear or parallel fashion. There are currently numerous combination regimens under investigation at either the preclinical or clinical levels, including histone deacetylase (HDAC) and CDK inhibitors; HDAC and proteasome inhibitors; HDAC and NF-kappaB (IKKbeta) inhibitors; CHK1 and MEK1/2 inhibitors; and BCL-2 antagonists and CDK inhibitors. Although combinations of targeted agents will not displace conventional cytotoxic regimens in AML or related disorders in the foreseeable future, these combinations clearly warrant further attention.
联合使用靶向药物治疗急性髓系白血病(AML)的概念是一个相对较新但具有潜在前景的研究领域。许多靶向药物单药活性可能有限,但与其他类型的类似化合物联合使用时可能显示出显著的前景。靶向药物联合使用可能以线性或平行方式有效中断多个信号通路。目前在临床前或临床水平有许多联合治疗方案正在研究中,包括组蛋白去乙酰化酶(HDAC)和细胞周期蛋白依赖性激酶(CDK)抑制剂;HDAC和蛋白酶体抑制剂;HDAC和核因子-κB(IKKβ)抑制剂;CHK1和MEK1/2抑制剂;以及BCL-2拮抗剂和CDK抑制剂。尽管在可预见的未来,靶向药物联合使用不会取代AML或相关疾病中的传统细胞毒性治疗方案,但这些联合治疗显然值得进一步关注。