Inhibition of autophagy enhances the anticancer effect of enzalutamide on bladder cancer

Quan, Yongjun; Lei, Hongen; Wahafu, Wasilijiang; Liu, Yuexin; Ping, Hao; Zhang, Xiaodong

doi:10.1016/j.biopha.2019.109490

Cited by 39 publications

(29 citation statements)

References 54 publications

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“…Additionally, Zheng et al [ 35 ] suggested that ATG5 inhibition contributed to treatment for esophageal carcinoma patients. Furthermore, autophagy abolition through the ATG5/7 re-sensitized EC109/CDDP knockdown or the use of pharmacological inhibitors is greatly significant [ 36 ] not only in the esophageal, but also in gastric [ 37 ], colorectal [ 38 , 39 ], bladder [ 40 ], ovarian [ 41 ], and prostate cancers [ 42 ]. With regard to TBK1, it has been proven that TBK1 takes part in modulating cell growth and autophagy [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of autophagy-related genes within esophageal carcinoma

Chen

Cao

et al. 2020

BMC Cancer

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Background: Several works suggest the importance of autophagy during esophageal carcinoma development. The aim of the study is to construct a scoring system according to the expression profiles of major autophagy-related genes (ARGs) among esophageal carcinoma cases. Methods: The Cancer Genome Atlas was employed to obtain the esophageal carcinoma data. Thereafter, the online database Oncolnc (http://www.oncolnc.org/) was employed to verify the accuracy of our results. According to our results, the included ARGs were related to overall survival (OS). Results: We detected the expression patterns of ARG within esophageal carcinoma and normal esophageal tissues. In addition, we identified the autophagy related gene set, including 14 genes displaying remarkable significance in predicting the esophageal carcinoma prognosis. The cox regression results showed that, 7 ARGs (including TBK1, ATG5, HSP90AB1, VAMP7, DNAJB1, GABARAPL2, and MAP2K7) were screened to calculate the ARGs scores. Typically, patients with higher ARGs scores were associated with poorer OS. Moreover, the receiver operating characteristic (ROC) curve analysis suggested that, ARGs accurately distinguished the healthy people from esophageal carcinoma patients, with the area under curve (AUC) value of > 0.6. Conclusion: A scoring system is constructed in this study based on the main ARGs, which accurately predicts the outcomes for esophageal carcinoma.

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Section: Discussionmentioning

confidence: 99%

Prognostic significance of autophagy-related genes within esophageal carcinoma

Chen

Cao

et al. 2020

BMC Cancer

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“…It has been shown that ULK1 can either promote or inhibit tumor growth through protein-protein interactions and post-translational modification-mediated autophagy in nutrient-deficient environments [24]. Thus, both the positive and negative regulation of ULK can situationally protect tumor cells from excessive autophagy [25]. ULK1 forms a protein complex together with the autophagy proteins mATG13, FIP200, and ATG101 to regulate the initiation of autophagy [26].…”

Section: Introductionmentioning

confidence: 99%

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

Liu

Liao

et al. 2020

Cancers

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The difficulty of early diagnosis and the development of drug resistance are two major barriers to the successful treatment of cancer. Autophagy plays a crucial role in several cellular functions, and its dysregulation is associated with both tumorigenesis and drug resistance. Unc-51-like kinase 1 (ULK1) is a serine/threonine kinase that participates in the initiation of autophagy. Many studies have indicated that compounds that directly or indirectly target ULK1 could be used for tumor therapy. However, reports of the therapeutic effects of these compounds have come to conflicting conclusions. In this work, we reviewed recent studies related to the effects of ULK1 on the regulation of autophagy and the development of drug resistance in cancers, with the aim of clarifying the mechanistic underpinnings of this therapeutic target.

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“…Likewise, the treatment of bladder cancer cells (J82 and T24) with enzalutamide, an anti-androgen receptor drug, resulted in cytoplasmatic autophagosomes accumulation, increased expression of autophagyrelated genes (AMPK, ATG5, LC3B, ULK1, and LC3-II) and had no effect on apoptosis and proliferation rates. However, the treatment with a combination of enzalutamide and autophagy inhibitors (CQ, 3-methyladenine, and bafilomycin A1) impaired tumor growth, indicating that the combined treatment may be a potential strategy to avoid enzalutamide-resistant bladder cancer (80). A similar result was exhibited in docetaxel resistant prostate cancer cell lines (PC3-DR and VCaP-DR): these cells present enhanced autophagy activity through the overexpression of Forkhead box protein M1 (FOXM1).…”

Section: Autophagy and Conventional Therapiesmentioning

confidence: 80%

The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

et al. 2020

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The tumor microenvironment (TME) is complex, and its composition and dynamics determine tumor fate. From tumor cells themselves, with their capacity for unlimited replication, migration, and invasion, to fibroblasts, endothelial cells, and immune cells, which can have pro and/or anti-tumor potential, interaction among these elements determines tumor progression. The understanding of molecular pathways involved in immune escape has permitted the development of cancer immunotherapies. Targeting molecules or biological processes that inhibit antitumor immune responses has allowed a significant improvement in cancer patient’s prognosis. Autophagy is a cellular process required to eliminate dysfunctional proteins and organelles, maintaining cellular homeostasis. Usually a process associated with protection against cancer, autophagy associated to cancer cells has been reported in response to hypoxia, nutrient deficiency, and oxidative stress, conditions frequently observed in the TME. Recent studies have shown a paradoxical association between autophagy and tumor immune responses. Tumor cell autophagy increases the expression of inhibitory molecules, such as PD-1 and CTLA-4, which block antitumor cytotoxic responses. Moreover, it can also directly affect antitumor immune responses by, for example, degrading NK cell-derived granzyme B and protecting tumor cells. Interestingly, the activation of autophagy on dendritic cells has the opposite effects, enhancing antigen presentation, triggering CD8+ T cells cytotoxic activity, and reducing tumor growth. Therefore, this review will focus on the most recent aspects of autophagy and tumor immune environment. We describe the dual role of autophagy in modulating tumor immune responses and discuss some aspects that must be considered to improve cancer treatment.

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Inhibition of autophagy enhances the anticancer effect of enzalutamide on bladder cancer

Cited by 39 publications

References 54 publications

Prognostic significance of autophagy-related genes within esophageal carcinoma

Prognostic significance of autophagy-related genes within esophageal carcinoma

A Review of ULK1-Mediated Autophagy in Drug Resistance of Cancer

The Role of Autophagy in Tumor Immunology—Complex Mechanisms That May Be Explored Therapeutically

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