Autophagy as a target for cancer therapy: new developments.
Autophagy as a target for cancer therapy: new developments.
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DOI：
10.2147/cmar.s26133
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发表时间：
2012
影响因子：
3.3
通讯作者：
Nawrocki ST
中科院分区：
文献类型：
--
作者：
Carew JS;Kelly KR;Nawrocki ST
自噬是一种进化上保守的溶酶体降解途径，它消除了胞浆蛋白、大分子、细胞器和蛋白质聚集体。自噬的激活可能通过降解有缺陷的细胞器和其他细胞成分而发挥肿瘤抑制作用。然而，这一途径也可能被癌细胞利用，在化疗引起的饥饿、缺氧和应激期间产生营养和能量。因此，诱导自噬已成为一种通过自我消化促进癌细胞存活的耐药机制。大量临床前研究表明，抑制自噬可以增强一系列抗癌药物的活性。因此，靶向自噬可能是一种全球性的抗癌策略，可能会提高许多标准护理药物的疗效。这些结果导致了多项临床试验，以评估自噬抑制与常规化疗相结合的效果。在这篇综述中，我们总结了已报道的调节自噬的抗癌药物，并讨论了抑制自噬作为抗癌策略的新进展。
Autophagy is an evolutionarily conserved lysosomal degradation pathway that eliminates cytosolic proteins, macromolecules, organelles, and protein aggregates. Activation of autophagy may function as a tumor suppressor by degrading defective organelles and other cellular components. However, this pathway may also be exploited by cancer cells to generate nutrients and energy during periods of starvation, hypoxia, and stress induced by chemotherapy. Therefore, induction of autophagy has emerged as a drug resistance mechanism that promotes cancer cell survival via self-digestion. Numerous preclinical studies have demonstrated that inhibition of autophagy enhances the activity of a broad array of anticancer agents. Thus, targeting autophagy may be a global anticancer strategy that may improve the efficacy of many standard of care agents. These results have led to multiple clinical trials to evaluate autophagy inhibition in combination with conventional chemotherapy. In this review, we summarize the anticancer agents that have been reported to modulate autophagy and discuss new developments in autophagy inhibition as an anticancer strategy.