Controversies in cancer stem cells: targeting embryonic signaling pathways.
Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways.
National Cancer Institute, Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, Investigational Drug Branch, Bethesda, MD 20852, USA.
Naoko
N
Takebe
S Percy
SP
Ivy
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D051880:Receptors, Notch