Max von Pettenkofer Institute & Gene Center, Virology, National Reference Center for Retroviruses, Faculty of Medicine, LMU München, Munich, Germany.
Leukemia. 2021 Feb;35(2):299-311. doi: 10.1038/s41375-020-01069-1. Epub 2020 Oct 29.
The effective treatment of acute myeloid leukemia (AML) is very challenging. Due to the immense heterogeneity of this disease, treating it using a "one size fits all" approach is ineffective and only benefits a subset of patients. Instead, there is a shift towards more personalized treatment based on the patients' genomic signature. This shift has facilitated the increased revelation of novel insights into pathways that lead to the survival and propagation of AML cells. These AML survival pathways are involved in drug resistance, evasion of the immune system, reprogramming metabolism, and impairing differentiation. In addition, based on the reports of enhanced clinical efficiencies when combining drugs or treatments, deeper investigation into possible pathways, which can be targeted together to increase treatment response in a wider group of patients, is warranted. In this review, not only is a comprehensive summary of targets involved in these pathways provided, but also insights into the potential of targeting these molecules in combination therapy will be discussed.
急性髓系白血病(AML)的有效治疗极具挑战性。由于这种疾病存在巨大的异质性,采用“一刀切”的方法进行治疗是无效的,只能使一部分患者受益。相反,人们正在转向更基于患者基因组特征的个性化治疗。这种转变促进了对导致 AML 细胞存活和增殖的途径的新见解的深入揭示。这些 AML 存活途径涉及耐药性、逃避免疫系统、重编程代谢和损害分化。此外,基于联合用药或治疗时增强临床疗效的报道,有必要更深入地研究可能的联合治疗靶点,以提高更广泛患者群体的治疗反应。在这篇综述中,不仅全面总结了这些途径中涉及的靶点,还讨论了联合治疗中靶向这些分子的潜力。