Обзорная статья

Autophagy in cancer development, immune evasion, and drug resistance

Xuegang NiuDepartment 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, ChinaQi Sheng YouDepartment of Oncological Surgery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province 150000, ChinaKejun HouShantou UniversityYu TianSchool of Public Health, Benedictine University, Lisle, IL 60532, USAPenghui WeiDepartment 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, ChinaYang ZhuDepartment 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, ChinaBin GaoDepartment 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, ChinaMilad AshrafizadehDepartment of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong 250000, ChinaAmir Reza ArefAlireza KalbasiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USAIsrael CañadasBlood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA, USAGautam SethiNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117600, SingaporeVinay TergaonkarLaboratory of NF-κB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A⁎STAR), 61 Biopolis Drive, Proteos, Singapore 138673, SingaporeLingzhi WangNUS Centre for Cancer Research (N2CR), Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117600, SingaporeYuanxiang LinDepartment 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. Electronic address: [email protected]Dezhi KangDepartment 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. Electronic address: [email protected]Daniel J. KlionskyLife Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. Electronic address: [email protected]

2024en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1016/j.drup.2024.101170

Цитирования и источники

Цитирований: 2Использованных источников: 0

Показатели — AkademScholar