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.