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      Ovarian cancer stem cells: still an elusive entity?

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      Molecular Cancer
      BioMed Central

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          Abstract

          The cancer stem cell (CSC) model proposes that tumor development and progression are fueled and sustained by undifferentiated cancer cells, endowed with self-renewal and tumor-initiating capacity. Ovarian carcinoma, based on its biological features and clinical evolution, appears as a prototypical example of CSC-driven disease. Indeed, ovarian cancer stem cells (OCSC) would account not only for the primary tumor growth, the peritoneal spread and the relapse, but also for the development of chemoresistance, thus having profound implication for the treatment of this deadly disease. In the last decade, an increasing body of experimental evidence has supported the existence of OCSC and their pathogenic role in the disease. Nevertheless, the identification of OCSC and the definition of their phenotypical and functional traits have proven quite challenging, mainly because of the heterogeneity of the disease and of the difficulties in establishing reliable biological models. A deeper understanding of OCSC pathobiology will shed light on the mechanisms that underlie the clinical behaviour of OC. In addition, it will favour the design of innovative treatment regimens that, on one hand, would counteract the resistance to conventional chemotherapy, and, on the other, would aim at the eradication of OC through the elimination of its CSC component.

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          Epithelial-mesenchymal transitions in development and disease.

          The epithelial to mesenchymal transition (EMT) plays crucial roles in the formation of the body plan and in the differentiation of multiple tissues and organs. EMT also contributes to tissue repair, but it can adversely cause organ fibrosis and promote carcinoma progression through a variety of mechanisms. EMT endows cells with migratory and invasive properties, induces stem cell properties, prevents apoptosis and senescence, and contributes to immunosuppression. Thus, the mesenchymal state is associated with the capacity of cells to migrate to distant organs and maintain stemness, allowing their subsequent differentiation into multiple cell types during development and the initiation of metastasis.
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            Evolution of the cancer stem cell model.

            Genetic analyses have shaped much of our understanding of cancer. However, it is becoming increasingly clear that cancer cells display features of normal tissue organization, where cancer stem cells (CSCs) can drive tumor growth. Although often considered as mutually exclusive models to describe tumor heterogeneity, we propose that the genetic and CSC models of cancer can be harmonized by considering the role of genetic diversity and nongenetic influences in contributing to tumor heterogeneity. We offer an approach to integrating CSCs and cancer genetic data that will guide the field in interpreting past observations and designing future studies. Copyright © 2014 Elsevier Inc. All rights reserved.
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              Ovarian cancer.

              Ovarian cancer is not a single disease and can be subdivided into at least five different histological subtypes that have different identifiable risk factors, cells of origin, molecular compositions, clinical features and treatments. Ovarian cancer is a global problem, is typically diagnosed at a late stage and has no effective screening strategy. Standard treatments for newly diagnosed cancer consist of cytoreductive surgery and platinum-based chemotherapy. In recurrent cancer, chemotherapy, anti-angiogenic agents and poly(ADP-ribose) polymerase inhibitors are used, and immunological therapies are currently being tested. High-grade serous carcinoma (HGSC) is the most commonly diagnosed form of ovarian cancer and at diagnosis is typically very responsive to platinum-based chemotherapy. However, in addition to the other histologies, HGSCs frequently relapse and become increasingly resistant to chemotherapy. Consequently, understanding the mechanisms underlying platinum resistance and finding ways to overcome them are active areas of study in ovarian cancer. Substantial progress has been made in identifying genes that are associated with a high risk of ovarian cancer (such as BRCA1 and BRCA2), as well as a precursor lesion of HGSC called serous tubal intraepithelial carcinoma, which holds promise for identifying individuals at high risk of developing the disease and for developing prevention strategies.
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                Author and article information

                Contributors
                ugo.cavallaro@ieo.it
                Journal
                Mol Cancer
                Mol. Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                20 March 2017
                20 March 2017
                2017
                : 16
                : 64
                Affiliations
                ISNI 0000 0004 1757 0843, GRID grid.15667.33, , Unit of Gynecological Oncology Research, European Institute of Oncology, ; Via G. Ripamonti 435, I-20141 Milan, Italy
                Author information
                http://orcid.org/0000-0002-0884-6460
                Article
                638
                10.1186/s12943-017-0638-3
                5360065
                28320418
                30b0d461-52d9-438a-9515-1336a809f9f5
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 13 December 2016
                : 13 March 2017
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100005010, Associazione Italiana per la Ricerca sul Cancro;
                Award ID: IG-14622
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100004435, Association for International Cancer Research;
                Award ID: 10-0091
                Award Recipient :
                Funded by: Fondazione Istituto Europeo di Oncologia
                Funded by: Italian Ministry of Health
                Award ID: Ricerca Corrente 2013-2015
                Funded by: FundRef http://dx.doi.org/10.13039/501100002803, Fondazione Cariplo;
                Award ID: 2008-2375
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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