Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.
Targeting Autophagy in Cancer: Update on Clinical Trials and Novel Inhibitors.
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DOI：
10.3390/ijms18061279
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发表时间：
2017-06-16
影响因子：
5.6
通讯作者：
Amaravadi RK
中科院分区：
文献类型：
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作者：
Chude CI;Amaravadi RK
真核生物使用自噬作为通过降解和回收细胞器和蛋白质来维持细胞内稳态的机制。这一过程有助于晚期癌症的增殖和存活。越来越多的临床前证据表明，靶向自噬可以增强许多癌症疗法的疗效。羟氯喹（HCQ）是唯一一种临床批准的自噬抑制剂，本系统综述主要关注HCQ在癌症临床试验中的应用。临床前试验表明，HCQ单独和联合治疗导致肿瘤缩小的增强。这为正在进行的多项涉及HCQ单独和与其他治疗组合的临床试验提供了基础。然而，由于其效力，仍然需要更有效和特异性的自噬抑制剂。临床前阶段有多种自噬抑制剂，处于不同的开发阶段。仍需要对HCQ和其他自噬抑制剂的机制进行进一步研究，以回答围绕这些药物最终将如何用于临床的问题。
Eukaryotes use autophagy as a mechanism for maintaining cellular homeostasis by degrading and recycling organelles and proteins. This process assists in the proliferation and survival of advanced cancers. There is mounting preclinical evidence that targeting autophagy can enhance the efficacy of many cancer therapies. Hydroxychloroquine (HCQ) is the only clinically-approved autophagy inhibitor, and this systematic review focuses on HCQ use in cancer clinical trials. Preclinical trials have shown that HCQ alone and in combination therapy leads to enhancement of tumor shrinkage. This has provided the base for multiple ongoing clinical trials involving HCQ alone and in combination with other treatments. However, due to its potency, there is still a need for more potent and specific autophagy inhibitors. There are multiple autophagy inhibitors in the pre-clinical stage at various stages of development. Additional studies on the mechanism of HCQ and other autophagy inhibitors are still required to answer questions surrounding how these agents will eventually be used in the clinic.