title: Cancer stem cells and chemosensitivity.
abstract: Cancer lethality is mainly due to the onset of distant metastases and refractoriness to chemotherapy. Thus, the development of molecular targeted agents that can restore or increase chemosensitivity will provide valuable therapeutic options for cancer patients. Growing evidence indicates that a cellular subpopulation with stem cell-like features, commonly referred to as cancer stem cells (CSCs), is critical for tumor generation and maintenance. Recent advances in stem cell biology are revealing that this cellular fraction shares many properties with normal adult stem cells and is able to propagate the parental tumor in animal models. CSCs seem to be protected against widely used chemotherapeutic agents by means of different mechanisms, such as a marked proficiency in DNA damage repair, high expression of ATP-binding cassette drug transporters, and activation of PI3K/AKT and Wnt pathways. Moreover, microenvironmental stimuli such as those involved in the epithelial-mesenchymal transition and hypoxia indirectly contribute to chemoresistance by inducing in cancer cells a stem-like phenotype. Understanding how CSCs overcome chemotherapy-induced death stimuli, and integrating such knowledge into clinical research methodology, has become a priority in the process of identifying innovative therapeutic strategies aimed at improving the outcome of cancer patients.
authors.affiliation: Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Maugeri-Saccà
authors.forename: Paolo
authors.initials: P
authors.lastname: Vigneri
authors.forename: Ruggero
authors.initials: R
authors.lastname: De Maria
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004260:DNA Repair; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000502:physiology; D016192:Resting Phase, Cell Cycle; D059016:Tumor Microenvironment / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents