Developmental signaling pathways in cancer stem cells of solid tumors

Background: The intricate regulation of several signaling pathways is essential for embryonic development and adult tissue homeostasis. Cancers commonly display aberrant activity within these pathways. A population of cells identified in several cancers, termed cancer stem cells (CSCs) show similar properties to normal stem cells and evidence suggests that altered developmental signaling pathways play an important role in maintaining CSCs and thereby the tumor itself. Scope of review: This review will focus on the roles of the Notch, Wnt and Hedgehog pathways in the brain, breast and colon cancers. We describe the roles these pathways play in normal tissue homeostasis through the regulation of stem cell fate in these three tissues, and the experimental evidence indicating that the role of these pathways in cancers of these is directly linked to CSCs. Major conclusions: A large body of evidence is accumulating to indicate that the deregulation of Notch, Wnt and Hedgehog pathways play important roles in both normal and cancer stem cells. We are only beginning to understand how these pathways interact, how they are coordinated during normal development and adult tissue homeostasis, and how they are deregulated during cancer. However, it is becoming increasingly clear that if we are to target CSCs therapeutically, it will likely be necessary to develop combination therapies. General significance: If CSCs are the driving force behind tumor maintenance and growth then understanding the molecular mechanisms regulating CSCs is essential. Such knowledge will contribute to better targeted therapies that could significantly enhance cancer treatments and patient survival. This article is part of a Special Issue entitled Biochemistry of Stem Cells. (C) 2012 Elsevier B.V. All rights reserved.