Targeting the Wnt Pathway in Cancer
The Wnt pathway is an evolutionarily conserved signaling network that is critical for mammalian development and adult tissue maintenance, and, importantly, hyperactivated in most human cancers. Almost two decades of study has confirmed that Wnt signaling
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Kathleen H. Goss Michael Kahn ●
Editors
Targeting the Wnt Pathway in Cancer
Editors Kathleen H. Goss, Ph.D. Department of Surgery University of Chicago 5841 South Maryland Ave. SBRI J557F/MC 5032 Chicago, IL 60637 [email protected]
Michael Kahn, Ph.D. Provost’s Professor of Medicine and Pharmacy Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research University of Southern California 1425 San Pablo, ZNI-533 Los Angeles, CA 90033 [email protected]
ISBN 978-1-4419-8022-9 e-ISBN 978-1-4419-8023-6 DOI 10.1007/978-1-4419-8023-6 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011920692 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
The first hint that the Wnt signaling pathway might be involved in cancer came in the 1980s when one of the integration sites of the Mouse Mammary Tumor Virus (MMTV) was mapped to Int-1, later renamed Wnt-1 for its homology to the wingless (Wg) Drosophila patterning gene. A second provocative link to cancer came in the mid-1990s when adenomatous polyposis coli (APC), a tumor suppressor gene already strongly associated with hereditary and sporadic colorectal cancer, was identified as a negative regulator of Wnt signaling. In the years that followed, researchers have uncovered many of the molecular details of pathway regulation and function in developmental systems and adult tissues and found a critical role for Wnt signaling in the stem cells of several tissue types. Moreover, Wnt pathway hyperactivation, or dysregulation of specific pathway components, has now been observed in almost 50% of all human cancers. Numerous genetic animal models have been generated and characterized that provide compelling evidence that pathway activation is necessary and sufficient for the pathogenesis of several tumor types. Importantly, these models also provide preclinical tools to test the efficacy of Wnt pathway antagonists in vivo. Recently, a major focus in the field has been to develop specific and effective Wnt pathway inhibitors, including small molecules and antibodies, for potential clinical use for colorectal cancer and other tumor types. In fact, nearly all levels or components of the pathway have been target
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