title: Heterogeneity of Cancer Stem Cells: Rationale for Targeting the Stem Cell Niche.
abstract: Malignancy is fuelled by distinct subsets of stem-like cells which persist under treatment and provoke drug-resistant recurrence. Eradication of these cancer stem cells has therefore become a prime objective for the development and design of novel classes of anti-cancer therapeutics with improved clinical efficacy. Here, we portray potentially clinically-relevant hallmarks of cancer stem cells and focus on their recently appreciated properties of cell variability and plasticity, both of which make them elusive targets for cancer therapies. We reason that this 'disguise in heterogeneity' has fundamental implications for clinical management and elaborate on rational strategies to combat this diversity and target a broad range of tumorigenic cells. We propose exploitation of cancer stem cell niche dependence as a promising approach to interfere with various, rather than few, cancer stem cell subsets and suggest cancer-associated fibroblasts as a prime microenvironmental target for tumor stemness-depleting intervention.
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland; Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Tyrolean Cancer Research Institute (TKFI), Innrain 66, 6020 Innsbruck, Austria. Electronic address: Maximilian.Boesch@kssg.ch.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Boesch
authors.affiliation: Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Tyrolean Cancer Research Institute (TKFI), Innrain 66, 6020 Innsbruck, Austria. Electronic address: Sieghart.Sopper@i-med.ac.at.
authors.forename: Sieghart
authors.initials: S
authors.lastname: Sopper
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: Alain.Zeimet@i-med.ac.at.
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: Daniel.Reimer@i-med.ac.at.
authors.forename: Daniel
authors.initials: D
authors.lastname: Reimer
authors.affiliation: Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria. Electronic address: Guenther.Gastl@i-med.ac.at.
authors.forename: Guenther
authors.initials: G
authors.lastname: Gastl
authors.affiliation: Institute of Immunobiology, Kantonsspital St. Gallen, Rorschacherstrasse 95, 9007 St. Gallen, Switzerland. Electronic address: Burkhard.Ludewig@kssg.ch.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.affiliation: Internal Medicine V, Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; Tyrolean Cancer Research Institute (TKFI), Innrain 66, 6020 Innsbruck, Austria; Medical Clinic III, Oncology, Hematology, Immunoncology and Rheumatology, University Clinic Bonn (UKB), Sigmund-Freud-Strasse 25, 53127 Bonn, Germany. Electronic address: Dominik.Wolf@ukb.uni-bonn.de.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wolf
mesh_terms: D000818:Animals; D006801:Humans; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D055153:Stem Cell Niche / Q000187:drug effects* / Q000502:physiology; D059016:Tumor Microenvironment / Q000187:drug effects
keywords: Cancer stem cell; cancer treatment; cancer-associated fibroblast; stem cell niche; tumor heterogeneity; tumor microenvironment