Autophagy and doxorubicin resistance in cancer

Chen, Chao; Lu, Lu; Yan, Shichao; Yi, Huimei; Yao, Hui; Wu, Di; He, Guangchun; Tao, Xiaojun; Deng, Xiyun

doi:10.1097/cad.0000000000000572

Cited by 147 publications

(106 citation statements)

References 101 publications

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“…[36,37] Notably, autophagy plays a role in cancer resistance to chemotherapy and modulation of its components may restore drug sensitivity. [38] Chloroquine and hydroxychloroquine…”

Section: ]mentioning

confidence: 99%

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Sultan¹,

Howard²,

Tbakhi³

2020

Preprint

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Drug repositioning offers an unmatched opportunity to offer novel therapeutics to treat SARS family of coronaviruses (SARS-FCoVs); an issue that became extremely urgent with the spreading of a novel virus with potential to threaten the lives of millions of people. Hereby, we analyzed a dataset of patients who presented with SARS during the 2003 outbreak. We established a gene signature that defines differential gene expression in patients who were sick with SARS vs. healthy controls and convalescent patients. We used a robust platform to conduct drug repositioning based on clustered gene expression and pathway enrichment to identify best matching drugs. We identified 55 agents of potential benefit. In most of these drugs we were able to establish a link to previous related research, use as antiviral, or at least a hypothetical role in treating SARS-FCoVs. Most notably, the heat shock protein 90 (hsp90) emerged as a major component that enables viruses to hijack infected cells through the process of autophagy. Almost half of the drugs identified could be linked to hsp90. As such, we propose using hsp90 inhibitors, mainly geldanamycin and its derivatives, to treat COVID-19.

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“…[36,37] Notably, autophagy plays a role in cancer resistance to chemotherapy and modulation of its components may restore drug sensitivity. [38] Chloroquine and hydroxychloroquine…”

Section: ]mentioning

confidence: 99%

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Sultan¹,

Howard²,

Tbakhi³

2020

Preprint

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“…The high expression of ATG5 is closely related to the poor prognosis and drug resistance of gastric cancer [19]. It has been found that the disease-free survival rate and the overall survival rate of patients in the Beclin 1 high expression group are significantly increased [20].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

Qiu

Sun

Wang

et al. 2020

Preprint

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Background: The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer.Methods: GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscpae software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 222 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinical features and prognostic gene signatures, a nomogram was established to predict individual survival probability.Results: GO analysis showed that the 38 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 38 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients. Conclusions:This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy. Affiliations

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“…Many studies have shown that autophagy protein is closely related to the prognosis of GC patients. The high expression of ATG5 is closely related to the poor prognosis and drug resistance of gastric cancer [19]. It has been found that the disease-free survival rate and the overall survival rate of patients in the Beclin 1 high expression group are signi cantly increased [20].…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

Qiu

Sun

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background : The purpose of this study is to perform bioinformatics analysis of autophagy-related genes in gastric cancer, and to construct a multi-gene joint signature for predicting the prognosis of gastric cancer. Methods : GO and KEGG analysis were applied for differentially expressed autophagy-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. In order to optimize the prognosis evaluation system of gastric cancer, we established a prognosis model integrating autophagy-related genes. We used single factor Cox proportional risk regression analysis to screen genes related to prognosis from 204 autophagy-related genes in The Atlas Cancer Genome (TCGA) gastric cancer cohort. Then, the generated genes were applied to the Least Absolute Shrinkage and Selection Operator (LASSO). Finally, the selected genes were further included in the multivariate Cox proportional hazard regression analysis to establish the prognosis model. According to the median risk score, patients were divided into high-risk group and low-risk group, and survival analysis was conducted to evaluate the prognostic value of risk score. Finally, by combining clinic-pathological features and prognostic gene signatures, a nomogram was established to predict individual survival probability. Results : GO analysis showed that the 28 differently expressed autophagy-related genes was enriched in cell growth, neuron death, and regulation of cell growth. KEGG analysis showed that the 28 differently expressed autophagy-related genes were related to platinum drug resistance, apoptosis and p53 signaling pathway. The risk score was constructed based on 4 genes (GRID2, ATG4D,GABARAPL2, CXCR4), and gastric cancer patients were significantly divided into high-risk and low-risk groups according to overall survival. In multivariate Cox regression analysis, risk score was still an independent prognostic factor (HR = 1.922, 95% CI = 1.573-2.349, P < 0.001). Cumulative curve showed that the survival time of patients with low-risk score was significantly longer than that of patients with high-risk score (P < 0.001). The external data GSE62254 proved that nomograph had a great ability to evaluate the prognosis of individual gastric cancer patients. Conclusions: This study provides a potential prognostic marker for predicting the prognosis of GC patients and the molecular biology of GC autophagy.

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Autophagy and doxorubicin resistance in cancer

Cited by 147 publications

References 101 publications

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Drug Repositioning Suggests a Role for the Heat Shock Protein 90 Inhibitor Geldanamycin in Treating COVID-19 Infection

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

Identification and Validation of an Individualized Autophagy-Clinical Prognostic Index in Gastric Cancer Patients

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