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Cancer Research 67, 1879, March 1, 2007. doi: 10.1158/0008-5472.CAN-06-3958
© 2007 American Association for Cancer Research
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Reviews

Notch Signaling, {gamma}-Secretase Inhibitors, and Cancer Therapy

Ie-Ming Shih and Tian-Li Wang

Departments of Gynecology, Oncology, and Pathology, Johns Hopkins Medical Institutions, Baltimore, Maryland

Requests for reprints: Tian-Li Wang, Johns Hopkins Medical Institutions, Cancer Research Building-II, Room 306, 1550 Orleans Street, Baltimore, Maryland 21231. Phone: 410-502-7774; Fax: 410-502-7943; E-mail: tlw{at}jhmi.edu.

The Notch signaling pathway represents a critical component in the molecular circuits that control cell fate during development. Aberrant activation of this pathway contributes to tumorigenesis. The role of Notch in human cancer has been highlighted recently by the presence of activating mutations and amplification of Notch genes in human cancer and by the demonstration that genes in the Notch signaling pathway could be potential therapeutic targets. It has become clear that one of the major therapeutic targets in the Notch pathway are the Notch receptors, in which {gamma}-secretase inhibitors prevent the generation of the oncogenic (intracellular) domain of Notch molecules and suppress the Notch activity. This review article summarizes the biological roles of Notch molecules in cancer development with special emphasis on the promise and challenges in applying {gamma}-secretase inhibitors as a new line of targeted therapeutic agents. [Cancer Res 2007;67(5):1879–82]




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Copyright © 2007 by the American Association for Cancer Research.