Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance.
Oridonin and its derivatives for cancer treatment and overcoming therapeutic resistance.
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DOI：
10.1016/j.gendis.2020.06.010
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发表时间：
2021-07
期刊：
影响因子：
6.8
通讯作者：
Shen Q
中科院分区：
文献类型：
--
作者：
Liu X;Xu J;Zhou J;Shen Q
癌症是全球范围内发病率和死亡率较高的疾病之一。化疗仍然是大多数癌症患者的主要治疗选择，包括患有进展性、转移性和复发性疾病的患者。迄今为止，数百种化疗药物被用于治疗各种癌症，然而，化疗相关毒性和获得性治疗耐药性在很大程度上阻碍了抗癌疗效和结果。天然产物（NP）冬凌草甲素因其抗癌功效而被广泛研究。最近，冬凌草甲素已被证明可以通过多种机制克服耐药性，其真正的靶点尚未确定。已经合成了数百种冬凌草甲素衍生物类似物（oridonalogs），并筛选出改善的效力、生物利用度和其他药物性质。特别地，已经针对冬凌草甲素测试了许多这些冬凌草甲素类似物的肿瘤生长抑制、克服治疗抗性的潜力和免疫调节。这篇简要的综述旨在总结这一领域的进展，以确定临床试验水平的候选药物，有望治疗进展性癌症和逆转耐药性。
Cancer is one of the diseases with high morbidity and mortality on a global scale. Chemotherapy remains the primary treatment option for most cancer patients, including patients with progressive, metastatic, and recurrent diseases. To date, hundreds of chemotherapy drugs are used to treat various cancers, however, the anti-cancer efficacy and outcomes are largely hampered by chemotherapy-associated toxicity and acquired therapeutic resistance. The natural product (NP) oridonin has been extensively studied for its anti-cancer efficacy. More recently, oridonin has been shown to overcome drug resistance through multiple mechanisms, with yet-to-be-defined bona fide targets. Hundreds of oridonin derivative analogs (oridonalogs) have been synthesized and screened for improved potency, bioavailability, and other drug properties. Particularly, many of these oridonalogs have been tested against oridonin for tumor growth inhibition, potential for overcoming therapeutic resistance, and immunity modulation. This concise review seeks to summarize the advances in this field in light of identifying clinical-trial level drug candidates with the promise for treating progressive cancers and reversing chemoresistance.
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