Title:Targeting Notch as a Therapeutic Approach for Human Malignancies
Volume: 23
Issue: 1
Author(s): Natalia Platonova, Elena Lesma, Andrea Basile, Monica Bignotto, Silvia Garavelli, Maria Teresa Palano, Adriana Moschini, Antonino Neri, Michela Colombo and Raffaella Chiaramonte
Affiliation:
Keywords:
Notch, Dll, Jagged, therapeutic target, clinical trial, apoptosis, proliferation.
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.
