Targeted Therapy Development in Acute Myeloid Leukemia.
Targeted Therapy Development in Acute Myeloid Leukemia.
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DOI：
10.3390/biomedicines11020641
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发表时间：
2023-02-20
期刊：
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
针对急性髓系白血病(AML)的治疗开发已经酝酿了50年，最近导致了多靶向治疗的批准。然而，对于能够提供长期缓解和治愈这种异质性疾病的分子治疗的需求仍然没有得到满足。以前，针对AML的亚型，主要是在复发和难治的情况下，开发了广泛的小分子药物；然而，耐药性破坏了这些作为单一疗法的长期疗效。最近，小分子文奈德与阿扎替丁联合应用，与化疗相比，提高了老年AML患者的缓解率和总存活率。然而，这种方案仍然受到细胞毒性的限制，并且不能治愈。因此，对于针对AML中特定异常的治疗方法的需求很高，同时保留正常细胞并消除引发白血病的细胞。尽管如此，这种异质疾病的复杂性阻碍了开发这些疗法的迫切需要，促使针对不同白血病发生机制的创新疗法的发展。本文综述了急性髓系白血病靶向治疗的发展和翻译前景，包括选择性和非选择性药物的开发。
Therapeutic developments targeting acute myeloid leukemia (AML) have been in the pipeline for five decades and have recently resulted in the approval of multiple targeted therapies. However, there remains an unmet need for molecular treatments that can deliver long-term remissions and cure for this heterogeneous disease. Previously, a wide range of small molecule drugs were developed to target sub-types of AML, mainly in the relapsed and refractory setting; however, drug resistance has derailed the long-term efficacy of these as monotherapies. Recently, the small molecule venetoclax was introduced in combination with azacitidine, which has improved the response rates and the overall survival in older adults with AML compared to those of chemotherapy. However, this regimen is still limited by cytotoxicity and is not curative. Therefore, there is high demand for therapies that target specific abnormalities in AML while sparing normal cells and eliminating leukemia-initiating cells. Despite this, the urgent need to develop these therapies has been hampered by the complexities of this heterogeneous disease, spurring the development of innovative therapies that target different mechanisms of leukemogenesis. This review comprehensively addresses the development of novel targeted therapies and the translational perspective for acute myeloid leukemia, including the development of selective and non-selective drugs.
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