title: Anti-Cancer Stem-like Cell Compounds in Clinical Development - An Overview and Critical Appraisal.
abstract: Cancer stem-like cells (CSC) represent a subpopulation of tumor cells with elevated tumor-initiating potential. Upon differentiation, they replenish the bulk of the tumor cell population. Enhanced tumor-forming capacity, resistance to antitumor drugs, and metastasis-forming potential are the hallmark traits of CSCs. Given these properties, it is not surprising that CSCs have become a therapeutic target of prime interest in drug discovery. In fact, over the last few years, an enormous number of articles describing compounds endowed with anti-CSC activities have been published. In the meanwhile, several of these compounds and also approaches that are not based on the use of pharmacologically active compounds (e.g., vaccination, radiotherapy) have progressed into clinical studies. This article gives an overview of these compounds, proposes a tentative classification, and describes their biological properties and their developmental stage. Eventually, we discuss the optimal clinical setting for these compounds, the need for biomarkers allowing patient selection, the redundancy of CSC signaling pathways and the utility of employing combinations of anti-CSC compounds and the therapeutic limitations posed by the plasticity of CSCs.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan , Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Marcucci
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, University of Milan , Milan , Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
authors.affiliation: Technologie Servier, Department of Synthesis , Orléans , France.
authors.forename: François
authors.initials: F
authors.lastname: Lefoulon
keywords: biomarkers; cancer stem-like cells; classification; clinical development; epithelial–mesenchymal transition; therapy