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      lncRNA and Mechanisms of Drug Resistance in Cancers of the Genitourinary System

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          Abstract

          Available systemic treatment options for cancers of the genitourinary system have experienced great progress in the last decade. However, a large proportion of patients eventually develop resistance to treatment, resulting in disease progression and shorter overall survival. Biomarkers indicating the increasing resistance to cancer therapies are yet to enter clinical routine. Long non-coding RNAs (lncRNA) are non-protein coding RNA transcripts longer than 200 nucleotides that exert multiple types of regulatory functions of all known cellular processes. Increasing evidence supports the role of lncRNAs in cancer development and progression. Additionally, their involvement in the development of drug resistance across various cancer entities, including genitourinary malignancies, are starting to be discovered. Consequently, lncRNAs have been suggested as factors in novel therapeutic strategies to overcome drug resistance in cancer. In this review, the existing evidences on lncRNAs and their involvement in mechanisms of drug resistance in cancers of the genitourinary system, including renal cell carcinoma, bladder cancer, prostate cancer, and testicular cancer, will be highlighted and discussed to facilitate and encourage further research in this field. We summarize a significant number of lncRNAs with proposed pathways in drug resistance and available reported studies.

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          Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer

          Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen (PSA) level are at high risk for metastasis. We hypothesized that enzalutamide, which prolongs overall survival among patients with metastatic, castration-resistant prostate cancer, would delay metastasis in men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising PSA level.
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            Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal

            Summary Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with metastatic ccRCC, including two cases sampledat post-mortem. Metastatic competence was afforded by chromosome complexity, and we identify 9p loss as a highly selected event driving metastasis and ccRCC-related mortality (p = 0.0014). Distinct patterns of metastatic dissemination were observed, including rapid progression to multiple tissue sites seeded by primary tumors of monoclonal structure. By contrast, we observed attenuated progression in cases characterized by high primary tumor heterogeneity, with metastatic competence acquired gradually and initial progression to solitary metastasis. Finally, we observed early divergence of primitive ancestral clones and protracted latency of up to two decades as a feature of pancreatic metastases.
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              The global burden of urinary bladder cancer: an update

              Bladder cancer is among the top ten most common cancer types in the world, with approximately 550,000 new cases annually. The highest burden of bladder cancer is currently falling on most developed communities across the globe. But with an anticipated shift in world demographics with growing and aging populations mainly on the African continent, and important shifts in exposure to different risk factors across the world, this is likely to change over the next decades. In this review, we provide an overview of the current incidence, mortality, prevalence, survival, risk factors and costs of bladder cancer worldwide.
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                Author and article information

                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                03 August 2020
                August 2020
                : 12
                : 8
                : 2148
                Affiliations
                [1 ]Research Unit of Non-Coding RNAs and Genome Editing in Cancer, Division of Clinical Oncology, Department of Medicine, Comprehensive Cancer Center Graz, Medical University of Graz, 8036 Graz, Austria; dominik.barth@ 123456medunigraz.at (D.A.B.); martin.pichler@ 123456medunigraz.at (M.P.)
                [2 ]Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; juracekjaroslav@ 123456gmail.com
                [3 ]Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, 62500 Brno, Czech Republic; on.slaby@ 123456gmail.com
                [4 ]Central European Institute of Technology, Masaryk University, 62500 Brno, Czech Republic
                [5 ]Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
                Author notes
                [* ]Correspondence: gcalin@ 123456mdanderson.org
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0003-0812-3024
                https://orcid.org/0000-0001-9945-2530
                https://orcid.org/0000-0002-8701-9462
                Article
                cancers-12-02148
                10.3390/cancers12082148
                7463785
                32756406
                5026ccb0-fe4c-4f10-a61f-8a5c63deac38
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 July 2020
                : 30 July 2020
                Categories
                Review

                lncrna,drug resistance,chemoresistance,prostate cancer,renal cell carcinoma,bladder cancer,seminoma

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