Notch receptors: Introduction

NOTCH signalling is a essential for development and the regulation of self-renewing tissues. Aberrant activation of the NOTCH pathway leads to deregulation of a range of cellular functions which ultimately drives oncogenic transformation (e.g. sustained proliferation, evasion of cell death, loss of differentiation capacity, invasion and metastasis) [1]. Inhibition of NOTCH pathway signalling has therefore emerged as a novel mechanism for therapeutic intervention in NOTCH-driven cancers [2]. A number of strategies have been developed that target NOTCH siganalling at different levels of the pathway; for example monoclonal antibodies that block the function of NOTCH ligands (e.g. demcizumab) or NOTCH receptors (e.g. tarextumab), small molecule γ-secretase inhibitors (e.g. PF-3084014) and inhibitors that block formation of the nuclear NOTCH transcriptional activation complex (e.g. CB-103).

References

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1. Kangsamaksin T, Tattersall IW, Kitajewski J. (2014) Notch functions in developmental and tumour angiogenesis by diverse mechanisms. Biochem. Soc. Trans., 42 (6): 1563-8. [PMID:25399571]

2. Sorrentino C, Cuneo A, Roti G. (2019) Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies. Mediterr J Hematol Infect Dis, 11 (1): e2019037. [PMID:31308913]

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