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Molecules 2018, 23(2), 431;

Taming the Notch Transcriptional Regulator for Cancer Therapy

Laboratory of Cancer Cell Biology, Candiolo Cancer Institute-FPO, IRCCS, Str. Prov. 142, 10060 Candiolo, TO, Italy
Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy
Department of Oncology, University of Torino, c/o IRCCS, S.P. 142, 10060 Candiolo, TO, Italy
Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), 34149 Trieste, Italy
Authors to whom correspondence should be addressed.
Received: 22 January 2018 / Revised: 12 February 2018 / Accepted: 13 February 2018 / Published: 15 February 2018
(This article belongs to the Special Issue Transcription Factors as Therapeutic Targets)
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Notch signaling is a highly conserved pathway in all metazoans, which is deeply involved in the regulation of cell fate and differentiation, proliferation and migration during development. Research in the last decades has shown that the various components of the Notch signaling cascade are either upregulated or activated in human cancers. Therefore, its downregulation stands as a promising and powerful strategy for cancer therapy. Here, we discuss the recent advances in the development of small molecule inhibitors, blocking antibodies and oligonucleotides that hinder Notch activity, and their outcome in clinical trials. Although Notch was initially identified as an oncogene, later studies showed that it can also act as a tumor suppressor in certain contexts. Further complexity is added by the existence of numerous Notch family members, which exert different activities and can be differentially targeted by inhibitors, potentially accounting for contradictory data on their therapeutic efficacy. Notably, recent evidence supports the rationale for combinatorial treatments including Notch inhibitors, which appear to be more effective than single agents in fighting cancer. View Full-Text
Keywords: Notch transcription complex; gamma secretase inhibitors; combination therapy; blocking antibody; clinical trials; combination therapy Notch transcription complex; gamma secretase inhibitors; combination therapy; blocking antibody; clinical trials; combination therapy

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Tamagnone, L.; Zacchigna, S.; Rehman, M. Taming the Notch Transcriptional Regulator for Cancer Therapy. Molecules 2018, 23, 431.

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