title: Targeting cancer stem cells by inhibiting Wnt, Notch, and Hedgehog pathways.
abstract: Tumor relapse and metastasis remain major obstacles for improving overall cancer survival, which may be due at least in part to the existence of cancer stem cells (CSCs). CSCs are characterized by tumorigenic properties and the ability to self-renew, form differentiated progeny, and develop resistance to therapy. CSCs use many of the same signaling pathways that are found in normal stem cells, such as Wnt, Notch, and Hedgehog (Hh). The origin of CSCs is not fully understood, but data suggest that they originate from normal stem or progenitor cells, or possibly other cancer cells. Therapeutic targeting of both CSCs and bulk tumor populations may provide a strategy to suppress tumor regrowth. Development of agents that target critical steps in the Wnt, Notch, and Hh pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of CSCs, the development of new anti-CSC therapeutic agents, and the complexity of potential CSC signaling cross-talk are described in this Review.
authors.affiliation: National Cancer Institute, Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, Investigational Drug Branch, EPN7131, 6130 Executive Boulevard, Rockville, Bethesda, MD 20852, USA.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takebe
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Harris
authors.forename: Ronald Q
authors.initials: RQ
authors.lastname: Warren
authors.forename: S Percy
authors.initials: SP
authors.lastname: Ivy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control*; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051880:Receptors, Notch; D051153:Wnt Proteins