title: Drug discovery approaches to target Wnt signaling in cancer stem cells.
abstract: Cancer stem cells (CSCs) represent a unique subset of cells within a tumor that possess self-renewal capacity and pluripotency, and can drive tumor initiation and maintenance. First identified in hematological malignancies, CSCs are now thought to play an important role in a wide variety of solid tumors such as NSCLC, breast and colorectal cancer. The role of CSCs in driving tumor formation illustrates the dysregulation of differentiation in tumorigenesis. The Wnt, Notch and Hedgehog (HH) pathways are developmental pathways that are commonly activated in many types of cancer. While substantial progress has been made in developing therapeutics targeting Notch and HH, the Wnt pathway has remained an elusive therapeutic target. This review will focus on the clinical relevance of the Wnt pathway in CSCs and tumor cell biology, as well as points of therapeutic intervention and recent advances in targeting Wnt/β-catenin signaling.
authors.affiliation: Oncology Drug Discovery, Research and Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Curtin
authors.forename: Matthew V
authors.initials: MV
authors.lastname: Lorenzi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051153:Wnt Proteins