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Autophagy in cancer development, immune evasion, and drug resistance.

作者信息

Niu Xuegang, You Qi, Hou Kaijian, Tian Yu, Wei Penghui, Zhu Yang, Gao Bin, Ashrafizadeh Milad, Aref Amir Reza, Kalbasi Alireza, Cañadas Israel, Sethi Gautam, Tergaonkar Vinay, Wang Lingzhi, Lin Yuanxiang, Kang Dezhi, Klionsky Daniel J

机构信息

Department of Neurosurgery, Neurosurgery Research Institute, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, China; Department of Neurosurgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China.

Department of Oncological Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province 150000, China.

出版信息

Drug Resist Updat. 2025 Jan;78:101170. doi: 10.1016/j.drup.2024.101170. Epub 2024 Nov 15.


DOI:10.1016/j.drup.2024.101170
PMID:39603146
Abstract

Macroautophagy/autophagy is a highly conserved evolutionary mechanism involving lysosomes for the degradation of cytoplasmic components including organelles. The constitutive, basal level of autophagy is fundamental for preserving cellular homeostasis; however, alterations in autophagy can cause disease pathogenesis, including cancer. The role of autophagy in cancer is particularly complicated, since this process acts both as a tumor suppressor in precancerous stages but facilitates tumor progression during carcinogenesis and later stages of cancer progression. This shift between anti-tumor and pro-tumor roles may be influenced by genetic and environmental factors modulating key pathways such as those involving autophagy-related proteins, the PI3K-AKT-MTOR axis, and AMPK, which often show dysregulation in tumors. Autophagy regulates various cellular functions, including metabolism of glucose, glutamine, and lipids, cell proliferation, metastasis, and several types of cell death (apoptosis, ferroptosis, necroptosis and immunogenic cell death). These multifaceted roles demonstrate the potential of autophagy to affect DNA damage repair, cell death pathways, proliferation and survival, which are critical in determining cancer cells' response to chemotherapy. Therefore, targeting autophagy pathways presents a promising strategy to combat chemoresistance, as one of the major reasons for the failure in cancer patient treatment. Furthermore, autophagy modulates immune evasion and the function of immune cells such as T cells and dendritic cells, influencing the tumor microenvironment and cancer's biological behavior. However, the therapeutic targeting of autophagy is complex due to its dual role in promoting survival and inducing cell death in cancer cells, highlighting the need for strategies that consider both the beneficial and detrimental effects of autophagy modulation in cancer therapy. Hence, both inducers and inhibitors of autophagy have been introduced for the treatment of cancer. This review emphasizes the intricate interplay between autophagy, tumor biology, and immune responses, offering insights into potential therapeutic approaches that deploy autophagy in the cancer suppression.

摘要

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[6]
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[9]
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