Bioactive natural products (NPs) may play a critical role in cancer progression by targeting nucleic acids and a wide array of proteins, including enzymes. Furthermore, a large number of derivatives (NPDs), including semi-synthetic products and pharmacophores from NPs, have been developed to enhance the solubility and stability of NPs. Acute myeloid leukemia (AML) is a poor-prognosis hematologic malignancy characterized by the clonal accumulation in the blood and bone marrow of myeloid progenitors with high proliferative capacity, survival and propagation abilities. A number of potential pathways and targets have been identified for development in AML, and include, but are not limited to, Fms-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenases resulting from genetic mutations, BCL2 family members, various signaling kinases and histone deacetylases, as well as tumor-associated antigens (such as CD13, CD33, P-gp). By targeting nucleic acids, FLT3 or CD33, several FDA-approved NPs and NPDs (i.e., cytarabine, anthracyclines, midostaurin, melphalan and calicheamicin linked to anti-CD33) are the major agents of upfront treatment of AML. However, the effective treatment of the disease remains challenging, in part due to the heterogeneity of the disease but also to the involvement of the bone marrow microenvironment and the immune system in favoring leukemic stem cell persistence. This review summarizes the current state of the art, and provides a summary of selected NPs/NPDs which are either entering or have been investigated in preclinical and clinical trials, alone or in combination with current chemotherapy. With multifaceted actions, these biomolecules may target all hallmarks of AML, including multidrug resistance and deregulated metabolism.
生物活性天然产物通过靶向核酸及多种蛋白质（包括酶类），可能在癌症进展中发挥关键作用。此外，为提升天然产物的溶解性与稳定性，已开发出大量衍生物，包括半合成产物及源自天然产物的药效团。急性髓系白血病是一种预后不良的血液系统恶性肿瘤，其特征为具有高增殖能力、强生存与扩散潜能的髓系祖细胞在血液和骨髓中克隆性积累。目前已在AML中发现多个可供开发的潜在通路与靶点，包括但不限于由基因突变产生的FMS样酪氨酸激酶3和异柠檬酸脱氢酶、BCL2家族成员、多种信号激酶和组蛋白去乙酰化酶，以及肿瘤相关抗原（如CD13、CD33、P-糖蛋白）。通过靶向核酸、FLT3或CD33，数种经FDA批准的天然产物及其衍生物（如阿糖胞苷、蒽环类药物、米哚妥林、美法仑以及与抗CD33抗体连接的卡奇霉素）已成为AML一线治疗的主要药物。然而，该疾病的有效治疗仍面临挑战，部分源于疾病异质性，也与骨髓微环境及免疫系统参与维持白血病干细胞持续存在有关。本综述总结了当前研究进展，系统梳理了已进入或已完成临床前及临床试验的精选天然产物/衍生物（单药或联合现有化疗方案）。这些生物分子通过多维度作用机制，可能靶向AML的所有特征性病理环节，包括多药耐药和代谢失调。
肿瘤(癌症)患者之家