Abstract
Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective (cell survival), cytotoxic (cell death), cytostatic (growth arrest), and nonprotective (no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental. That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.
摘要
癌症是目前全世界的主要死亡原因之一. 药物在癌症的治疗过程中起着关键作用, 但癌细胞本身复杂的生物学过程严重限制了各种抗癌药物的疗效. 自噬作为一种维持细胞内环境稳态的自我降解系统, 普遍存在于正常和应激条件下的癌细胞中. 然而, 自噬在癌症治疗中的角色却存在争议, 因为诱导和抑制自噬都可以增强抗癌药物的疗效. 因此, 在癌症治疗过程中, 我们应该诱导还是抑制自噬就成为了一个重要的问题. 目前, 根据自噬在癌症治疗中的不同功能, 可以将其分为四种主要形式: 细胞保护性 (细胞存活) 自噬、细胞毒性 (细胞死亡) 自噬、 生长抑制性 (生长停滞) 自噬和非保护性 (对细胞死亡和存活均无影响) 自噬. 此外, 药物是通过诱导各种各样的细胞死亡方式发挥抗癌作用的, 如凋亡、 坏死、 铁死亡、 细胞衰老和有丝分裂灾难等. 然而, 自噬和这些细胞死亡方式之间的相互作用是复杂的, 这将可能导致抗癌药物对治疗产生不同甚至完全相反的效果. 因此, 了解抑制或诱导自噬在何种情况下是有益还是有害的就非常重要. 也就是说, 应该根据自噬的不同功能采取相应的治疗策略. 这篇综述总结了近年来自噬与癌症治疗之间关系的最新见解, 可为临床抗癌药物的应用提供新思路.
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This work was supported by the National Natural Science Foundation of China (No. 81903642), the China Postdoctoral Science Foundation (No. 2020M681528), the Postdoctoral Science Foundation of Jiangsu Province (No. 2021K369C), the Jiangsu Cancer Hospital Postdoctoral Science Foundation (No. SZL202015), the Basic Scientific Research Business Expense Project of China Pharmaceutical University (No. 2632021ZD07), and the Project Funded by the Priority Academic Program Development (PADP) of Jiangsu Higher Education Institutions, China.
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Zhaoshi BAI and Lingman MA designed the review. Zhaoshi BAI, Yaling PENG, Xinyue YE, Zhixian LIU, and Yupeng LI searched references. Zhaoshi BAI, Yaling PENG, and Lingman MA collated and summarized references. Zhaoshi BAI, Yaling PENG, and Lingman MA wrote the manuscript. All authors approved the final manuscript.
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Zhaoshi BAI, Yaling PENG, Xinyue YE, Zhixian LIU, Yupeng LI, and Lingman MA declare that they have no conflict of interest.
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Bai, Z., Peng, Y., Ye, X. et al. Autophagy and cancer treatment: four functional forms of autophagy and their therapeutic applications. J. Zhejiang Univ. Sci. B 23, 89–101 (2022). https://doi.org/10.1631/jzus.B2100804
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DOI: https://doi.org/10.1631/jzus.B2100804