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.

中文翻译：

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急性髓系白血病治疗进展：新药和新挑战。

在过去几年中，急性髓性白血病 (AML) 的治疗设备迅速扩大，这主要是由于对其基因组景观的转化研究和对传统疗法耐药机制的深入了解。然而，对于大多数患者来说，原发性和继发性耐药性仍然是一个重大问题。对这些新药耐药机制的研究正在为下一类​​ AML 药物的开发和旨在优化利用治疗弱点的联合方案设计提供信息，最终目标是根除该疾病的所有亚克隆并提高治愈率反洗钱。意义：AML 是一种异质性疾病，其特点是广泛的分子改变影响临床结果，也为药物开发提供了潜在的靶点。本综述讨论了当前和新兴的 AML 治疗前景，重点介绍了新型药物，以及我们对耐药机制的深入了解如何为未来的治疗提供信息，并为有效的联合策略提供新的机会。