Urinary bladder cancer: biomarkers and target therapy, new era for more attention

Mohammed, Amrallah A.; EL-Tanni, Hani; EL-Khatib, Hani M.; Mirza, Ahmad A.; Mirza, Abdulrahim A.; Alturaifi, Turki H.

doi:10.4081/oncol.2016.320

Cited by 28 publications

(27 citation statements)

References 63 publications

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“…Even the most effective neoadjuvant chemotherapy produces favorable responses in only about 25% of BC patients . Few advances in the treatment of BC have been found in recent decades . Therefore, a novel effective treatment strategy is urgently required in the management of BC.…”

Section: Introductionmentioning

confidence: 99%

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Tian

Jiang

et al. 2018

Cancer Science

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Neddylation has been researched in many different human carcinomas. However, the roles of neural precursor cell expressed, developmentally downregulated 8 (NEDD8) in bladder cancer are still unknown. Our study was the first study which systematically investigated the possible functions of NEDD8 in bladder cancer (BC) progression. We carried out immunohistochemistry to explore associations between the expression of NEDD8 in tumor tissues and clinical outcomes of patients. RT‐qPCR and western blot were used to detect the expressional levels of genes. The biological abilities of cell proliferation, migration and invasion were researched by in vitro and in vivo experiments. Results were as follows: Data from The Cancer Genome Atlas (TCGA) database showed that NEDD8 was overexpressed in BC tissues and was associated with poor patient survival. Results of immunohistochemistry found that NEDD8 was significantly associated with poor clinical outcomes of BC patients. Suppression of NEDD8 could inhibit the proliferation, migration and invasion of tumor cells. Knocking down NEDD8 could induce apoptosis and G2 phase arrest of cell cycle progression. In vivo, suppression of NEDD8 restricted growth and metastasis of tumors in mice. In conclusion, NEDD8 has important roles in regulating the progression of BC cells and was associated with poor prognosis of patients; hence, it may become a potential therapeutic target of BC.

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Section: Introductionmentioning

confidence: 99%

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Tian

Jiang

et al. 2018

Cancer Science

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“…The holistic vision of cancer, including histopathology, omics, cancer microenvironment, and interactions with the immune system, could determine a more accurate prognosis [25,26]. Despite attempts to improve the predictive capacity of the tumor-node-metastasis (TNM) staging system [2,27], or to introduce mutational, transcriptional, and epigenetic analyses [26], significant variations in the outcome of patients with similar BC status still remain, underling the need for new clinically relevant…”

Section: Discussionmentioning

confidence: 99%

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Guillamón

Gimeno

Server

et al. 2021

European Urology Oncology

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“…81% of patients demonstrated progressive disease and the median survival time was 3 months (Petrylak et al, 2010). Almost all anti-angiogenic agents as sunitinib, pazopanib, aflibercept and ramucirumab have been evaluated in multiple settings in UC, without clear clinical benefit (Mohammed et al, 2016). These trials failed mostly due to lack of biomarkers.…”

Section: Treatment Of Bladder Cancermentioning

confidence: 99%

Functional Genomics Identifies Multiple Clinically Actionable Resistance Mechanisms to CDK4/6 Inhibition in Bladder Cancer

et al. 2019

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angenommen AFFIDAVIT I hereby declare that the dissertation titled Functional genomics identifies multiple clinical actional resistance mechanisms to CDK4/6 inhibition in bladder cancer prepared under the guidance and supervision of Univ.-Prof. Dr. Jürgen E. Gschwend at the Department of Urology and submitted to the degree-awarding institution of: The Faculty of Medicine of TUM is my own, original work undertaken in partial fulfillment of the requirements for the doctoral degree. I have made no use of sources, materials or assistance other than those specified in § 6 (6) and (7), clause 2. AbstractThough CDK4/6 inhibition has already been proven as a promising approach for the treatment of bladder cancer in preclinical research. However, mechanisms of resistance still are unclear. Therefore, a genome-scale CRISPR-dCas9 gain of function screen for the CDK4/6 inhibitor Palbociclib was performed in the bladder cancer derived cell line T24. Enrichment of sgRNAs were detected using NGS and statistically significant sgDNAs from the screen were analyzed using MAGeCK-VISPR. 1024 sgRNAs encoding for 995 genes were significantly enriched in the screen. In order to validate these data, 8 randomly chosen sgRNAs within the first most significant 500 sgRNAs were functionally validated on a molecular and functional level for mediating resistance to Palbociclib treatment. Comparison of the screen hits to signaling pathways and clinically relevant molecular alterations was performed using DAVID, Reactome, DGIdb and and cBioPortal. We identified enriched sgRNAs in RTKs, PI3K-Akt and Ras/MAPK signaling pathways that are also frequently activated in bladder cancer. Combination of Palbociclib with compounds directed against RTKs, PI3K-Akt, Ras/MAPK and STAT pathways revealed beneficial effects in vitro and in vivo xenografts. Since activation of the signalingpathways that confer resistance are largely regulated by RTKs, we engineered cells that by sgRNA induced hyperactivation of KDR or FGFR3 mediated resistance to palbociclib. Interestingly, in these cells the combination of Palbociclib and respective inhibitors acted synergistically and overcame acquired resistance in those tumors. However, the combination of Palbociclib and mTOR inhibitors did not overcome the induced resistance of KDR or FGFR3 expression. In conclusion, identification of resistance mechanisms and rational combinational therapies could be achieved applying a genome scale CRISPR-dCas9 approach in this study.

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Urinary bladder cancer: biomarkers and target therapy, new era for more attention

Cited by 28 publications

References 63 publications

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Neural precursor cell expressed, developmentally downregulated 8 promotes tumor progression and predicts poor prognosis of patients with bladder cancer

Immunological Risk Stratification of Bladder Cancer Based on Peripheral Blood Natural Killer Cell Biomarkers

Functional Genomics Identifies Multiple Clinically Actionable Resistance Mechanisms to CDK4/6 Inhibition in Bladder Cancer

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