靶向FLT3突变在急性髓系白血病中的作用:奎兹替尼在精准医学中的作用。

Q4 Medicine
Manoj Kumbhare, Siddhi Chandak, Bhagwan Ide, Aishwarya Dukare, Sakshi Velhal, Harshali Gode, Nishant Pagere, Arshad Shaikh
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引用次数: 0

摘要

急性髓性白血病(AML)是一种遗传异质性的血液恶性肿瘤,不成比例地影响老年人。在各种基因改变中,FLT3内腱重复(FLT3- itd)突变存在于大约20-30%的患者中,并与疾病的快速进展和频繁复发有关。本综述评估了第二代高选择性FLT3抑制剂quizartinib作为复发或难治性AML的靶向治疗选择的作用。临床前研究表明,quizarinib具有有效抑制FLT3信号,良好的药代动力学特性和高生物利用度的作用。早期临床试验报告了FLT3-ITD突变患者有希望的缓解率,而III期研究进一步证实了其疗效,显示单独使用或与标准化疗一起使用时总生存率提高。尽管取得了这些进展,但quizartinib的临床应用仍受到诸如获得性耐药、脱靶效应(包括QT间期延长)和复杂的药物-药物相互作用等挑战的限制。正在进行的研究集中在阐明耐药机制和开发有效的联合方案,以优化其治疗潜力。总体而言,quizartinib代表了AML精准医学的重大突破,为改善这一具有挑战性疾病的患者预后提供了一条有希望的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting FLT3 Mutations in Acute Myeloid Leukemia: The Role of Quizartinib in Precision Medicine.

Acute Myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy that disproportionately affects older individuals. Among the various genetic alterations, FLT3 internal tendem duplication (FLT3-ITD) mutations are present in approximately 20-30% of patients and are linked to rapid disease progression and frequent relapses. This review evaluates the role of quizartinib, a second-generation, highly selective FLT3 inhibitor, as a targeted therapeutic option for relapsed or refractory AML. Preclinical studies have demonstrated that quizartinib offers potent inhibition of FLT3 signaling, favorable pharmacokinetic properties, and high bioavailability. Early-phase clinical trials reported promising remission rates in patients harboring FLT3-ITD mutations, while phase III studies further substantiated its efficacy by showing improved overall survival when used alone or alongside standard chemotherapy. Despite these advances, quizartinib's clinical use is limited by challenges such as acquired resistance, off-target effects-including QT interval prolongation-and complex drug-drug interactions. Ongoing research is focused on elucidating resistance mechanisms and developing effective combination regimens to optimize its therapeutic potential. Overall, quizartinib represents a significant breakthrough in precision medicine for AML, offering a promising avenue to improve patient outcomes in this challenging disease.

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CiteScore
0.70
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