Paola Rizzo, Donato Mele, Cristiana Caliceti, Micaela Pannella, Cinzia Fortini, Anthony George Clementz, Marco Bruno Morelli, Giorgio Aquila, Pietro Ameri, Roberto Ferrari
Abstract
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.
Pharmacology, Toxicology and Pharmaceutical Science
6
10%
Neuroscience
3
5%
Other
7
12%
Unknown
8
14%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 5. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 04 July 2022.
All research outputs
#7,120,776
of 25,932,719 outputs
Outputs from Frontiers in oncology
#2,358
of 22,839 outputs
Outputs of similar age
#87,333
of 362,984 outputs
Outputs of similar age from Frontiers in oncology
#22
of 99 outputs
Altmetric has tracked 25,932,719 research outputs across all sources so far. This one has received more attention than most of these and is in the 72nd percentile.
So far Altmetric has tracked 22,839 research outputs from this source. They receive a mean Attention Score of 3.1. This one has done well, scoring higher than 89% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 362,984 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 75% of its contemporaries.
We're also able to compare this research output to 99 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 77% of its contemporaries.
