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The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors
Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells, which are considered responsible for tumo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292456/ https://www.ncbi.nlm.nih.gov/pubmed/25629006 http://dx.doi.org/10.3389/fonc.2014.00384 |
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author | Rizzo, Paola Mele, Donato Caliceti, Cristiana Pannella, Micaela Fortini, Cinzia Clementz, Anthony George Morelli, Marco Bruno Aquila, Giorgio Ameri, Pietro Ferrari, Roberto |
author_facet | Rizzo, Paola Mele, Donato Caliceti, Cristiana Pannella, Micaela Fortini, Cinzia Clementz, Anthony George Morelli, Marco Bruno Aquila, Giorgio Ameri, Pietro Ferrari, Roberto |
author_sort | Rizzo, Paola |
collection | PubMed |
description | Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells, which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta-like ligand 4 (Dll4)-activated Notch signaling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long-term cardiotoxicity associated to Notch inhibition in cancer patients. In this review, we will focus on mechanisms through which inhibition of Notch signaling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor. |
format | Online Article Text |
id | pubmed-4292456 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42924562015-01-27 The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors Rizzo, Paola Mele, Donato Caliceti, Cristiana Pannella, Micaela Fortini, Cinzia Clementz, Anthony George Morelli, Marco Bruno Aquila, Giorgio Ameri, Pietro Ferrari, Roberto Front Oncol Oncology Targeting the Notch pathway is a new promising therapeutic approach for cancer patients. Inhibition of Notch is effective in the oncology setting because it causes a reduction of highly proliferative tumor cells and it inhibits survival of cancer stem cells, which are considered responsible for tumor recurrence and metastasis. Additionally, since Delta-like ligand 4 (Dll4)-activated Notch signaling is a major modulator of angiogenesis, anti-Dll4 agents are being investigated to reduce vascularization of the tumor. Notch plays a major role in the heart during the development and, after birth, in response to cardiac damage. Therefore, agents used to inhibit Notch in the tumors (gamma secretase inhibitors and anti-Dll4 agents) could potentially affect myocardial repair. The past experience with trastuzumab and other tyrosine kinase inhibitors used for cancer therapy demonstrates that the possible cardiotoxicity of agents targeting shared pathways between cancer and heart and the vasculature should be considered. To date, Notch inhibition in cancer patients has resulted only in mild gastrointestinal toxicity. Little is known about the potential long-term cardiotoxicity associated to Notch inhibition in cancer patients. In this review, we will focus on mechanisms through which inhibition of Notch signaling could lead to cardiomyocytes and endothelial dysfunctions. These adverse effects could contrast with the benefits of therapeutic responses in cancer cells during times of increased cardiac stress and/or in the presence of cardiovascular risk factor. Frontiers Media S.A. 2015-01-13 /pmc/articles/PMC4292456/ /pubmed/25629006 http://dx.doi.org/10.3389/fonc.2014.00384 Text en Copyright © 2015 Rizzo, Mele, Caliceti, Pannella, Fortini, Clementz, Morelli, Aquila, Ameri and Ferrari. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Rizzo, Paola Mele, Donato Caliceti, Cristiana Pannella, Micaela Fortini, Cinzia Clementz, Anthony George Morelli, Marco Bruno Aquila, Giorgio Ameri, Pietro Ferrari, Roberto The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title | The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title_full | The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title_fullStr | The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title_full_unstemmed | The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title_short | The Role of Notch in the Cardiovascular System: Potential Adverse Effects of Investigational Notch Inhibitors |
title_sort | role of notch in the cardiovascular system: potential adverse effects of investigational notch inhibitors |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4292456/ https://www.ncbi.nlm.nih.gov/pubmed/25629006 http://dx.doi.org/10.3389/fonc.2014.00384 |
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