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Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349363/ https://www.ncbi.nlm.nih.gov/pubmed/32575680 http://dx.doi.org/10.3390/cells9061503 |
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author | Moore, Gillian Annett, Stephanie McClements, Lana Robson, Tracy |
author_facet | Moore, Gillian Annett, Stephanie McClements, Lana Robson, Tracy |
author_sort | Moore, Gillian |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7349363 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-73493632020-07-22 Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives Moore, Gillian Annett, Stephanie McClements, Lana Robson, Tracy Cells Review 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. MDPI 2020-06-20 /pmc/articles/PMC7349363/ /pubmed/32575680 http://dx.doi.org/10.3390/cells9061503 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Moore, Gillian Annett, Stephanie McClements, Lana Robson, Tracy Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title | Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title_full | Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title_fullStr | Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title_full_unstemmed | Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title_short | Top Notch Targeting Strategies in Cancer: A Detailed Overview of Recent Insights and Current Perspectives |
title_sort | top notch targeting strategies in cancer: a detailed overview of recent insights and current perspectives |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7349363/ https://www.ncbi.nlm.nih.gov/pubmed/32575680 http://dx.doi.org/10.3390/cells9061503 |
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