Taming the Notch Transcriptional Regulator for Cancer Therapy

Luca Tamagnone, Serena Zacchigna, Michael Rehman

Risultato della ricerca: Contributo in rivistaArticolo in rivistapeer review

23 Citazioni (Scopus)

Abstract

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.
Lingua originaleEnglish
pagine (da-a)1-17
Numero di pagine17
RivistaMolecules
Volume23
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Blocking antibody
  • Clinical trials
  • Combination therapy
  • Gamma secretase inhibitors
  • Notch transcription complex
  • clinical trials
  • combination therapy

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