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当代肿瘤药物靶点

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

PPARγ激动剂在联合癌症治疗中的作用

卷 20, 期 3, 2020

页: [197 - 215] 页: 19

弟呕挨: 10.2174/1568009619666191209102015

价格: $65

摘要

过氧化物酶体增殖物激活的受体-γ(PPARγ)是一种核受体,其作为转录因子参与能量代谢,细胞周期,细胞分化和细胞凋亡的调控。这些独特的性质构成了强大的治疗潜力,这使PPARγ激动剂成为最有趣和研究最广泛的抗癌分子之一。尽管PPARγ激动剂在体外具有显着的抗增殖和杀肿瘤活性,但它们在动物模型中的抗癌作用尚不明确,并且在单药疗法的临床试验中效果不理想。然而,由于正常和肿瘤细胞中PPARγ活化的多效性作用,PPARγ配体与许多抗肿瘤治疗方式相互作用,并协同增强其有效性。最引人注目的例子是慢性粒细胞白血病(CML)中PPARγ配体与酪氨酸激酶抑制剂(TKIs)的组合。在这种情况下,PPARγ激活可使对任何先前治疗形式有抵抗力的白血病干细胞对靶向治疗敏感。因此,该组合被认为是能够治愈CML患者的第一种药理疗法。在过去十年中,已经发表了大量数据,证实了将PPARγ配体添加到包括化学疗法,激素疗法,靶向疗法和免疫疗法在内的各种抗肿瘤疗法中的益处。尽管这些研究大多数是在体外或动物肿瘤模型中进行的,但最近已进行了一些成功的尝试,将PPARγ配体引入人体的抗癌治疗。在这篇综述中,我们旨在总结抗肿瘤治疗中靶向PPARγ的亮点和阴影。

关键词: 过氧化物酶体增殖物激活受体-γ,PPARγ配体,噻唑烷二酮,癌症,白血病,联合疗法,酪氨酸激酶抑制剂,伊马替尼。

图形摘要

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