Division of Hematology, Medical Oncology and Palliative Care, Department of Medicine, University of Wisconsin-Madison, 1111 Highland Ave, Madison, WI, 53705-2281, USA.
J Hematol Oncol. 2024 Nov 18;17(1):113. doi: 10.1186/s13045-024-01632-8.
The AML treatment landscape has significantly changed in recent years with the approval of targeted therapies in the front-line and relapsed/refractory settings, including inhibitors of FLT3 and IDH1/2 mutations. More importantly, approval of the combination of the BCl-2 inhibitor, venetoclax, and hypomethylating agents or low dose cytarabine provided unprecedented breakthrough for the frontline treatment of older, unfit AML patients. Even with all this exciting progress, more targeted therapies for AML treatment are needed. Recent development of menin inhibitors targeting AML with KMT2A rearrangements or NPM1 mutations could represent a promising new horizon of treatment for patients within these subsets of AML. Our current review will focus on a summary and updates of recent developments of menin inhibitors in the treatment of AML, on the challenges ahead arising from drug resistance, as well as on the opportunities of novel combinations with menin inhibitors.
近年来，随着针对一线和复发/难治性疾病的靶向治疗药物（包括 FLT3 和 IDH1/2 突变抑制剂）的批准，AML 的治疗格局发生了重大变化。更重要的是，BCL-2 抑制剂维奈托克与低剂量阿糖胞苷或去甲基化药物联合应用的批准，为年龄较大、不适合治疗的 AML 患者的一线治疗提供了前所未有的突破。尽管取得了所有这些令人兴奋的进展，但 AML 的治疗仍需要更多的靶向治疗药物。最近开发的针对 KMT2A 重排或 NPM1 突变的 AML 的门冬酰胺酶抑制剂，可能为这些 AML 亚群的患者提供了一个有前途的新治疗方向。我们目前的综述将重点介绍门冬酰胺酶抑制剂在 AML 治疗中的最新研究进展、耐药性带来的挑战，以及与门冬酰胺酶抑制剂的新联合应用的机会。
