title: Cancer stem cells in colorectal cancer from pathogenesis to therapy: controversies and perspectives.
abstract: Colorectal cancer remains one of the most common and lethal malignancies worldwide despite the use of various therapeutic strategies. A better understanding of the mechanisms responsible for tumor initiation and progression is essential for the development of novel, more powerful therapies. The traditional, so-called "stochastic model" of tumor development, which assumes that each cancer cell is tumorigenic, has been deeply challenged during the past decade by the identification of cancer stem cells (CSCs), a biologically distinct subset of cells within the bulk of tumor mass. This discovery led to the development of the hierarchical model of tumorigenesis which assumes that only CSCs have the ability to initiate tumor growth, both at primary and metastatic sites. This model implies that the elimination of all CSCs is fundamental to eradicate tumors and that failure to do so might be responsible for the occurrence of relapses and/or metastases frequently observed in the clinical management of colorectal cancer patients. Identification and isolation of CSCs is essential for a better understanding of their role in the tumorigenetic process and for the development of CSC-specific therapies. Several methods have been used for this purpose and many efforts have been focused on the identification of specific CSC-surface markers. This review provides an overview of the proposed roles of CSC in human colorectal tumorigenesis focusing on the most important molecules identified as CSC-specific markers in colorectal cancer and on the potential strategies for the development of CSC-targeted therapy.
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fanali
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Lucchetti
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Marisa
authors.initials: M
authors.lastname: Farina
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Corbi
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Cufino
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Achille
authors.initials: A
authors.lastname: Cittadini
authors.affiliation: Caterina Fanali, Donatella Lucchetti, Marisa Farina, Maddalena Corbi, Valerio Cufino, Achille Cittadini, Alessandro Sgambato, Istituto di Patologia Generale, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor
keywords: Cancer stem cells; Cancer therapy; Colorectal cancer; Prognostic marker; Tumorigenesis