Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.

Moore, G; Annett, S; McClements, L; Robson, T

Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.

Moore, G Annett, S McClements, L

Robson, T

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Cells, 2020, 9, (6)
Issue Date:: 2020-06-20

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Field	Value	Language
dc.contributor.author	Moore, G
dc.contributor.author	Annett, S
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.contributor.author	Robson, T
dc.date.accessioned	2020-10-20T03:26:14Z
dc.date.available	2020-06-11
dc.date.available	2020-10-20T03:26:14Z
dc.date.issued	2020-06-20
dc.identifier.citation	Cells, 2020, 9, (6)
dc.identifier.issn	2073-4409
dc.identifier.issn	2073-4409
dc.identifier.uri	http://hdl.handle.net/10453/143396
dc.description.abstract	Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Cells
dc.relation.isbasedon	10.3390/cells9061503
dc.rights	info:eu-repo/semantics/openAccess
dc.title	Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives.
dc.type	Journal Article
utslib.citation.volume	9
utslib.location.activity	Switzerland
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.date.updated	2020-10-20T03:26:03Z
pubs.issue	6
pubs.publication-status	Published
pubs.volume	9
utslib.citation.issue	6

Abstract:

Evolutionarily conserved Notch plays a critical role in embryonic development and cellular self-renewal. It has both tumour suppressor and oncogenic activity, the latter of which is widely described. Notch-activating mutations are associated with haematological malignancies and several solid tumours including breast, lung and adenoid cystic carcinoma. Moreover, upregulation of Notch receptors and ligands and aberrant Notch signalling is frequently observed in cancer. It is involved in cancer hallmarks including proliferation, survival, migration, angiogenesis, cancer stem cell renewal, metastasis and drug resistance. It is a key component of cell-to-cell interactions between cancer cells and cells of the tumour microenvironment, such as endothelial cells, immune cells and fibroblasts. Notch displays diverse crosstalk with many other oncogenic signalling pathways, and may drive acquired resistance to targeted therapies as well as resistance to standard chemo/radiation therapy. The past 10 years have seen the emergence of different classes of drugs therapeutically targeting Notch including receptor/ligand antibodies, gamma secretase inhibitors (GSI) and most recently, the development of Notch transcription complex inhibitors. It is an exciting time for Notch research with over 70 cancer clinical trials registered and the first-ever Phase III trial of a Notch GSI, nirogacestat, currently at the recruitment stage.

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http://hdl.handle.net/10453/143396