Identification and validation of a novel autophagy gene expression signature for human bladder cancer patients

Eissa, Sanaa; Matboli, Marwa; Awad, Nahla; Kotb, Yousif

doi:10.1177/1010428317698360

Cited by 20 publications

(17 citation statements)

References 32 publications

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“…The authors of this study suggested that the unique autophagy gene expression signature may serve as a novel, clinically useful biomarker for predicting response to tyrosine kinase inhibitor therapy. Eissa et al [ 118 ] identified and validated a novel autophagy transcript signature for the diagnosis of human bladder cancer. In this study, the expression levels of a number of autophagy genes, including ATG12 and ULK1, in paired bladder tissue and urine samples were significantly lower in bladder cancer than in the control group.…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers

Bortnik

Gorski

2017

IJMS

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Autophagy, a lysosome-mediated intracellular degradation and recycling pathway, plays multiple context-dependent roles in tumorigenesis and treatment resistance. Encouraging results from various preclinical studies have led to the initiation of numerous clinical trials with the intention of targeting autophagy in various cancers. Accumulating knowledge of the particular mechanisms and players involved in different steps of autophagy regulation led to the ongoing discovery of small molecule inhibitors designed to disrupt this highly orchestrated process. However, the development of validated autophagy-related biomarkers, essential for rational selection of patients entering clinical trials involving autophagy inhibitors, is lagging behind. One possible source of biomarkers for this purpose is the autophagy machinery itself. In this review, we address the recent trends, challenges and advances in the assessment of the biomarker potential of clinically relevant autophagy proteins in human cancers.

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Section: Discussion and Future Directionsmentioning

confidence: 99%

Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers

Bortnik

Gorski

2017

IJMS

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“…Alterations in expression of various key autophagy genes have been reported for different types of cancer, including breast, lung, pancreatic, bladder cancer, and leukemia . As mentioned above, one of the common molecular aberrations is the loss of one of the alleles of the essential autophagy gene Beclin‐1.…”

Section: Part I: the Role Of Autophagy In Cancer Cellsmentioning

confidence: 99%

The multifaceted role of autophagy in cancer and the microenvironment

Folkerts

Hilgendorf

Vellenga

et al. 2018

Medicinal Research Reviews

159

143

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Autophagy is a crucial recycling process that is increasingly being recognized as an important factor in cancer initiation, cancer (stem) cell maintenance as well as the development of resistance to cancer therapy in both solid and hematological malignancies. Furthermore, it is being recognized that autophagy also plays a crucial and sometimes opposing role in the complex cancer microenvironment. For instance, autophagy in stromal cells such as fibroblasts contributes to tumorigenesis by generating and supplying nutrients to cancerous cells. Reversely, autophagy in immune cells appears to contribute to tumor‐localized immune responses and among others regulates antigen presentation to and by immune cells. Autophagy also directly regulates T and natural killer cell activity and is required for mounting T‐cell memory responses. Thus, within the tumor microenvironment autophagy has a multifaceted role that, depending on the context, may help drive tumorigenesis or may help to support anticancer immune responses. This multifaceted role should be taken into account when designing autophagy‐based cancer therapeutics. In this review, we provide an overview of the diverse facets of autophagy in cancer cells and nonmalignant cells in the cancer microenvironment. Second, we will attempt to integrate and provide a unified view of how these various aspects can be therapeutically exploited for cancer therapy.

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“…Examples include CDKN2B, PIK3CA, BRCA2, NFkB, ARHGEF4, XPA, NCOA4, MDC1, UBR5, RB1CC1, RPS6, CIITA, MITF, and WT1 (16,54,64,69,(88)(89)(90)(91)(92)(93). It is anticipated that other shared molecular targets will be found.…”

Section: Other Molecular Featuresmentioning

confidence: 99%

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

et al. 2020

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There is a great need to improve the outlook for people facing urinary bladder cancer, especially for patients with invasive urothelial carcinoma (InvUC) which is lethal in 50% of cases. Improved outcomes for patients with InvUC could come from advances on several fronts including emerging immunotherapies, targeted therapies, and new drug combinations; selection of patients most likely to respond to a given treatment based on molecular subtypes, immune signatures, and other characteristics; and prevention, early detection, and early intervention. Progress on all of these fronts will require clinically relevant animal models for translational research. The animal model(s) should possess key features that drive success or failure of cancer drugs in humans including tumor heterogeneity, genetic-epigenetic crosstalk, immune cell responsiveness, invasive and metastatic behavior, and molecular subtypes (e.g., luminal, basal). Experimental animal models, while essential in bladder cancer research, do not possess these collective features to accurately predict outcomes in humans. These key features, however, are present in naturally-occurring InvUC in pet dogs. Canine InvUC closely mimics muscle-invasive bladder cancer in humans in cellular and molecular features, molecular subtypes, immune response patterns, biological behavior (sites and frequency of metastasis), and response to therapy. Thus, dogs can offer a highly relevant animal model to complement other models in research for new therapies for bladder cancer. Clinical treatment trials in pet dogs with InvUC are considered a win-win-win scenario; the individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to translate to better treatment outcomes in humans. In addition, the high breedassociated risk for InvUC in dogs (e.g., 20-fold increased risk in Scottish Terriers) Knapp et al. Canine Bladder Cancer-Translational Model offers an unparalleled opportunity to test new strategies in primary prevention, early detection, and early intervention. This review will provide an overview of canine InvUC, summarize the similarities (and differences) between canine and human InvUC, and provide evidence for the expanding value of this canine model in bladder cancer research.

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Identification and validation of a novel autophagy gene expression signature for human bladder cancer patients

Cited by 20 publications

References 32 publications

Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers

Clinical Applications of Autophagy Proteins in Cancer: From Potential Targets to Biomarkers

The multifaceted role of autophagy in cancer and the microenvironment

Naturally-Occurring Invasive Urothelial Carcinoma in Dogs, a Unique Model to Drive Advances in Managing Muscle Invasive Bladder Cancer in Humans

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