Targeting notch as a therapeutic approach for human malignancies

Natalia Platonova, Elena Lesma, Andrea Basile, Monica Bignotto, Silvia Garavelli, Maria Teresa Palano, Adriana Moschini, Antonino Neri, Michela Colombo, Raffaella Chiaramonte

Research output: Contribution to journalReview article

Abstract

Background: Notch is a multifaceted protein that plays a fundamental role in fetal development and tissue homeostasis by directing many cellular functions, including cell growth and differentiation, cell fate determination and regulation of stem cells maintenance. The Notch family consists of four receptors (Notch 1-4) and five ligands (Jagged1-2 and Delta-like 1-3-4) widely expressed in human tissues. Given the crucial contribution of Notch signaling in many physiological processes, it is not surprising that a variety of human malignancies is characterized by a dysregulation of one or more components of this pathway. Methods: In this review, we are going to provide a broad overview on the role of Notch pathway in solid and hematological malignancies and a survey on possible Notch-directed therapeutic strategies. Results: We present the most recent findings indicating that Notch signaling dysregulation in human cancers may be due to genetic and epigenetic alterations or to the interactions with other oncogenic pathways. Furthermore, Notch activity may have an oncogenic or a tumor suppressor effect. Finally, we describe the latest preclinical and clinical studies concerning the different pharmacological approaches targeting Notch. Conclusion: The provided evidence confirms the importance of Notch pathway in human malignancies indicating that a strong rationale exists for the development of a Notch-tailored therapy.

Original languageEnglish
Pages (from-to)108-134
Number of pages27
JournalCurrent Pharmaceutical Design
Volume23
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Keywords

  • Apoptosis
  • Clinical trial
  • Dll
  • Jagged
  • Notch
  • Proliferation
  • Therapeutic target

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

Cite this

Platonova, N., Lesma, E., Basile, A., Bignotto, M., Garavelli, S., Palano, M. T., Moschini, A., Neri, A., Colombo, M., & Chiaramonte, R. (2017). Targeting notch as a therapeutic approach for human malignancies. Current Pharmaceutical Design, 23(1), 108-134. https://doi.org/10.2174/1381612822666161006160524