title: Targeting cancer stem cells for more effective therapies: Taking out cancer's locomotive engine.
abstract: Novel therapies for the treatment of solid tumors have generally failed to improve patient overall survival. These therapeutic approaches are typically focused on targeting signaling pathways implicated in cell growth and/or survival in order to shrink the malignant mass and achieve an objective clinical response; however, too often these responses are followed by eventual regrowth of the tumor. This clinical conundrum could be explained by the existence of a tumorigenic cell population that is relatively resistant to these therapies and retains pluripotent status in order to repopulate the original tumor and/or contribute to distant metastasis following treatment. Compelling data from liquid tumors, and more recently from studies focused on solid tumors, now support the existence of such tumorigenic cells (i.e., cancer stem cells) as a distinct subpopulation within the total tumor cell mass. These cancer stem cells (CSCs), as compared to the non-CSC population, have the ability to reconstitute the primary tumor phenotype when transplanted into recipient animals. In addition, data are beginning to emerge demonstrating that many standard-of-care chemotherapeutics are less effective in promoting cell death or cytostasis in these putative cancer stem cells as compared to effects in the non-stem cell cancerous cells. Therefore, targeting these locomotive drivers of tumors, the cancer stem cell population, should be considered a high priority in the continued pursuit of more effective cancer therapies.
authors.affiliation: Department of Pharmacology, Vertex Pharmaceuticals Inc., 130 Waverly Street, Cambridge, MA 02139, USA. raymond_winquist@vrtx.com
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Winquist
authors.forename: Diane M
authors.initials: DM
authors.lastname: Boucher
authors.forename: Mark
authors.initials: M
authors.lastname: Wood
authors.forename: Brinley F
authors.initials: BF
authors.lastname: Furey
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000473:pathology; D016503:Drug Delivery Systems; D015195:Drug Design; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D009369:Neoplasms / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins