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      Determinants of metastatic competency in colorectal cancer

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          Abstract

          Colorectal cancer ( CRC) is one of the most common cancer types and represents a major therapeutic challenge. Although initial events in colorectal carcinogenesis are relatively well characterized and treatment for early‐stage disease has significantly improved over the last decades, the mechanisms underlying metastasis – the main cause of death – remain poorly understood. Correspondingly, no effective therapy is currently available for advanced or metastatic disease. There is increasing evidence that colorectal cancer is hierarchically organized and sustained by cancer stem cells, in concert with various stromal cell types. Here, we review the interplay between cancer stem cells and their microenvironment in promoting metastasis and discuss recent insights relating to both patient prognosis and novel targeted treatment strategies. A better understanding of these topics may aid the prevention or reduction of metastatic burden.

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          Tumor metastasis: molecular insights and evolving paradigms.

          Metastases represent the end products of a multistep cell-biological process termed the invasion-metastasis cascade, which involves dissemination of cancer cells to anatomically distant organ sites and their subsequent adaptation to foreign tissue microenvironments. Each of these events is driven by the acquisition of genetic and/or epigenetic alterations within tumor cells and the co-option of nonneoplastic stromal cells, which together endow incipient metastatic cells with traits needed to generate macroscopic metastases. Recent advances provide provocative insights into these cell-biological and molecular changes, which have implications regarding the steps of the invasion-metastasis cascade that appear amenable to therapeutic targeting. Copyright © 2011 Elsevier Inc. All rights reserved.
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            A genetic model for colorectal tumorigenesis.

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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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                Author and article information

                Contributors
                Daniele.Tauriello@irbbarcelona.org
                ACalon@imim.es
                Eduard.Batlle@irbbarcelona.org
                Journal
                Mol Oncol
                Mol Oncol
                10.1002/(ISSN)1878-0261
                MOL2
                Molecular Oncology
                John Wiley and Sons Inc. (Hoboken )
                1574-7891
                1878-0261
                03 January 2017
                January 2017
                : 11
                : 1 , Cancer metastasis ( doiID: 10.1002/mol2.2017.11.issue-1 )
                : 97-119
                Affiliations
                [ 1 ] Institute for Research in Biomedicine (IRB Barcelona) The Barcelona Institute of Science and Technology Spain
                [ 2 ] Hospital del Mar Medical Research Institute (IMIM) Barcelona Spain
                [ 3 ] Institució Catalana de Recerca i Estudis Avançats (ICREA) Barcelona Spain
                Author notes
                [*] [* ] Correspondence

                D. V. F. Tauriello, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri i Reixac 10, 08028 Barcelona, Spain

                E‐mail: Daniele.Tauriello@ 123456irbbarcelona.org

                A. Calon, Hospital del Mar Medical Research Institute (IMIM), MAR Health Park Barcelona, Dr. Aiguader, 88, 08003, Barcelona, Spain

                E‐mail: ACalon@ 123456imim.es

                and

                E. Batlle, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri I Reixac 10, 08028 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Pg. Lluis Companys 23, 08010 Barcelona, Spain

                E‐mail: Eduard.Batlle@ 123456irbbarcelona.org

                Article
                MOL212018
                10.1002/1878-0261.12018
                5423222
                28085225
                62c1e39a-76e8-4e98-814e-8952feedf1d0
                © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 August 2016
                : 30 September 2016
                : 21 October 2016
                Page count
                Figures: 3, Tables: 0, Pages: 23, Words: 16271
                Funding
                Funded by: Spanish Ministry of Economy and Competitiveness (MINECO)
                Award ID: SAF2014‐53784_R
                Funded by: Fundación Olga Torres
                Funded by: Asociación Española contra el Cáncer
                Funded by: Dr. Josef Steiner Foundation
                Funded by: Fundación Botín
                Funded by: Banco Santander
                Categories
                Review Article
                Review Articles
                Custom metadata
                2.0
                mol212018
                January 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.4 mode:remove_FC converted:25.07.2017

                Oncology & Radiotherapy
                cancer immunology,cancer stem cells,clonal diversity,combination therapy,dormancy,heterogeneity,immunotherapy,stroma,tgf‐beta,tumour microenvironment

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