Stanford University School of Medicine, Stanford, CA 94305-5821, USA.
Int J Hematol. 2012 Aug;96(2):178-85. doi: 10.1007/s12185-012-1151-5. Epub 2012 Aug 6.
Although complete remissions can be achieved in most patients younger than 60 years of age with untreated acute myeloid leukemia (AML), only 30-40 % of patients remain long-term survivors. Furthermore, long-term survivors represent only 10-15 % of all AML patients older than 60 years of age and <10 % of all patients with relapsed AML. The development of new treatments for AML is therefore needed. Novel therapies should target specific mechanisms and pathways implicated in the development and maintenance of AML, should strive to have better tolerability than conventional combination chemotherapy, be associated with improved quality of life and minimize utilization of health care resources. In this manuscript, we discuss the role of epigenetic regulators and immunomodulatory agents in the treatment of AML. Also, we review the data on inhibitors of protein homeostasis and its synergistic effect to DNA methyltransferase inhibitors, the potential role for inhibitors of heat shock proteins and the mitotic machinery and a novel formulation of conventional chemotherapeutic agents given at a fixed molar concentration. Finally, we briefly share our views on optimal clinical trial design and patient selection for future studies in AML.
尽管未经治疗的急性髓细胞白血病（AML）患者中年龄小于 60 岁的大多数患者可达到完全缓解，但只有 30-40%的患者可长期生存。此外，长期生存者仅占所有年龄大于 60 岁的 AML 患者的 10-15%和所有复发性 AML 患者的<10%。因此，需要开发新的 AML 治疗方法。新型疗法应针对 AML 发生和维持中涉及的特定机制和途径，应努力比传统联合化疗具有更好的耐受性，与改善生活质量相关，并最大限度地减少对医疗资源的利用。在本文中，我们讨论了表观遗传调节剂和免疫调节剂在 AML 治疗中的作用。此外，我们还回顾了蛋白动态平衡抑制剂及其与 DNA 甲基转移酶抑制剂协同作用的数据、热休克蛋白和有丝分裂机制抑制剂的潜在作用，以及固定摩尔浓度的常规化疗药物的新型制剂。最后，我们简要分享了我们对 AML 未来研究中最佳临床试验设计和患者选择的看法。
