title: Tumor-Initiating Cells: a criTICal review of isolation approaches and new challenges in targeting strategies.
abstract: Most cancers contain a subpopulation of highly tumorigenic cells, known as cancer stem cells (CSCs) or tumor-initiating cells (TICs). Targeting TICs may be essential to achieve cure, because of their self-renewal and tumorigenic properties as well as their resistance to conventional therapies. Despite significant advances in TIC biology, their isolation and identification remain largely disputed and incompletely established. In this review, we discuss the latest developments in isolation and culturing approaches of TICs, with focus on colorectal cancer (CRC). We feature recent findings on TIC-relevant signaling pathways and the metabolic identity of TICs, as well as their current clinical implications. Lastly, we highlight the influence of inter- and intra-tumoral heterogeneity on TIC function and targeting approaches.
authors.affiliation: Life Sciences Research Unit, Molecular Disease Mechanisms Group, University of Luxembourg, 6, Avenue du Swing, L-4367, Campus Belval, Belvaux, Luxembourg.
authors.forename: Komal
authors.initials: K
authors.lastname: Qureshi-Baig
authors.affiliation: Life Sciences Research Unit, Molecular Disease Mechanisms Group, University of Luxembourg, 6, Avenue du Swing, L-4367, Campus Belval, Belvaux, Luxembourg.
authors.forename: Pit
authors.initials: P
authors.lastname: Ullmann
authors.affiliation: Life Sciences Research Unit, Molecular Disease Mechanisms Group, University of Luxembourg, 6, Avenue du Swing, L-4367, Campus Belval, Belvaux, Luxembourg.
authors.forename: Serge
authors.initials: S
authors.lastname: Haan
authors.affiliation: Life Sciences Research Unit, Molecular Disease Mechanisms Group, University of Luxembourg, 6, Avenue du Swing, L-4367, Campus Belval, Belvaux, Luxembourg. elisabeth.letellier@uni.lu.
authors.forename: Elisabeth
authors.identifier: 0000-0001-8242-9393
authors.initials: E
authors.lastname: Letellier
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D018740:Genetic Heterogeneity; D006801:Humans; D058990:Molecular Targeted Therapy; D014411:Neoplastic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor
keywords: Cancer stem cells; Colorectal cancer; Culturing conditions; Inter- and intra-tumor heterogeneity; Metabolic identity; Spheroid Culture Systems; Surface markers; Targeted therapy; Tumor-initiating cells