Journal
SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY
Volume 23, Issue 4, Pages 465-472Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.semcdb.2012.01.016
Keywords
Notch; Cancer; T-ALL; gamma-Secretase; Inhibitor
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Funding
- NIH from National Institute of General Medical Sciences (NIGMS) [R01 GM087650]
- Thomas Jefferson University Department of Biochemistry
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Dysregulated Notch signaling has been implicated in numerous human diseases, including a broad spectrum of cancers. Mutations in Notch1 are prevalent in T-cell acute lymphoblastic leukemia, and abnormal expression of different human Notch receptors contributes to B-cell tumors as well as cancers of the breast, lung, pancreas, skin, prostate, colon, brain and other tissues. Several gamma-secretase inhibitors, small chemical compounds that were initially developed to inhibit the activity of the gamma-secretase aspartyl protease in Alzheimer's disease, are now being explored for their potential chemotherapeutic applications in Notch-associated cancers. An alternative approach involves the development of antibodies to inhibit specific Notch receptors, their activating ligands, or other components of the Notch pathway in tumors. Here we review recent progress and current challenges in the use of these strategies to modulate Notch signaling for cancer therapy. (C) 2012 Elsevier Ltd. All rights reserved.
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