Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments

Horne, G. A. and Copland, M. (2017) Approaches for targeting self-renewal pathways in cancer stem cells: implications for hematological treatments. Expert Opinion on Drug Discovery, 12(5), pp. 465-474. (doi: 10.1080/17460441.2017.1303477) (PMID:28277836)

Abstract

Introduction: Self-renewal is considered a defining property of stem cells. Self-renewal is essential in embryogenesis and normal tissue repair and homeostasis. However, in cancer, self-renewal pathways, e.g. WNT, NOTCH, Hedgehog and BMP, frequently become de-regulated in stem cells, or more mature progenitor cells acquire self-renewal properties, resulting in abnormal tissue growth and tumorigenesis. Areas covered: This review considers the conserved embryonic self-renewal pathways, including WNT, NOTCH, Hedgehog and BMP. The article describes recent advances in our understanding of these pathways in leukemia and, more specifically, leukemia stem cells (LSC), how these pathways cross-talk and interact with the LSC microenvironment, and discusses the clinical implications and potential therapeutic strategies, both in preclinical and in clinical trials for hematological malignancies. Expert opinion: The conserved embryonic self-renewal pathways are frequently de-regulated in cancer stem cells (CSC), including LSCs. There is significant cross-talk between self-renewal pathways, and their downstream targets, and the microenvironment. Effective targeting of these pathways is challenging due to cross-talk, and importantly, because these pathways are important for normal stem cells as well as CSC, adverse effects on normal tissues may mean a therapeutic window cannot be identified. Nonetheless, several agents targeting these pathways are currently in clinical trials in hematological malignancies.

• Item Type: Articles
• Additional Information: The authors are supported by the University of Glasgow and the Wellcome Trust.
• Keywords: Hedgehog, NOTCH, self-renewal, WNT, bone morphogenic protein, cancer stem cell, leukemia stem cell, microenvironment.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Horne, Dr Gillian and Copland, Professor Mhairi
• Authors: Horne, G. A., and Copland, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Expert Opinion on Drug Discovery
• Publisher: Taylor & Francis
• ISSN: 1746-0441
• ISSN (Online): 1746-045X
• Published Online: 06 March 2017
• Copyright Holders: Copyright © 2017 Informa UK Limited, trading as Taylor & Francis Group
• First Published: First published inExpert Opinion on Drug Discovery 12(5):465-474
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher