Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Discov. 2020 Apr;10(4):506-525. doi: 10.1158/2159-8290.CD-19-1011. Epub 2020 Feb 3.
The therapeutic armamentarium of acute myeloid leukemia (AML) has rapidly expanded in the past few years, driven largely by translational research into its genomic landscape and an improved understanding of mechanisms of resistance to conventional therapies. However, primary and secondary drug resistance remains a substantial problem for most patients. Research into the mechanisms of resistance to these new agents is informing the development of the next class of AML drugs and the design of combination regimens aimed at optimally exploiting therapeutic vulnerabilities, with the ultimate goal of eradicating all subclones of the disease and increasing cure rates in AML. SIGNIFICANCE: AML is a heterogeneous disease, characterized by a broad spectrum of molecular alterations that influence clinical outcomes and also provide potential targets for drug development. This review discusses the current and emerging therapeutic landscape of AML, highlighting novel classes of drugs and how our expanding knowledge of mechanisms of resistance are informing future therapies and providing new opportunities for effective combination strategies.
在过去的几年中，急性髓系白血病（AML）的治疗方法迅速扩展，这主要得益于对其基因组图谱的转化研究和对常规治疗耐药机制的深入理解。然而，大多数患者仍然存在原发性和继发性耐药问题。对这些新药物耐药机制的研究为下一代 AML 药物的开发和旨在充分利用治疗弱点的联合治疗方案的设计提供了信息，最终目标是消除疾病的所有亚克隆并提高 AML 的治愈率。
AML 是一种异质性疾病，其特征是广泛的分子改变，影响临床结局，并为药物开发提供潜在靶点。本综述讨论了 AML 的当前和新兴治疗领域，强调了新型药物类别，以及我们对耐药机制的不断增长的认识如何为未来的治疗方法提供信息，并为有效的联合策略提供新的机会。
