Cardiovascular ramifications of therapy-induced endothelial cell senescence in cancer survivors

Abstract

Cancer survivorship has remarkably improved over the past decades; nevertheless, cancer survivors are burdened with multiple health complications primarily caused by their cancer therapy. Therapy-induced senescence is recognized as a fundamental mechanism contributing to adverse health complications in cancer survivors. In this mini-review, we will discuss the recent literature describing the mechanisms of cancer therapy-induced senescence. We will focus on endothelial cell senescence since it has been shown to be a key player in numerous cardiovascular complications. We will also discuss novel senotherapeutic approaches that have the potential to combat therapy-induced endothelial cell senescence.

Keywords: Anthracyclines; Cancer therapy; Cardio-oncology; Endothelial cells; Radiation; Senescence.

Fig. 1.. Cancer therapy-induced senescence in endothelial cells.

Exposure of the vasculature to cancer treatments including radiation and anthracyclines induces senescence in endothelial cells. Multiple mechanisms contribute to the senescence phenotype in endothelial cells, which demonstrate characteristic alterations. Accumulation of senescent endothelial cells leads to endothelial dysfunction, which contributes to cardiovascular diseases in cancer survivors. Senotherapeutics are novel drugs that target cancer therapy-induced endothelial senescence either by targeting SASP (senomorphics) or by inducing apoptosis in senescent endothelial cells (senolytics). The figure is created with BioRender.com. eNOS, endothelial nitric oxide synthase; ET1, Endothelin-1; NAC, N-acetyl cysteine; NO, Nitric oxide; PAI-1, Plasminogen activator inhibitor-1; PGI2, prostacyclin; SA-β-gal, Senescence associated-βgalactosidase assay; SAHF, Senescence-associated heterochromatin foci; SASP, Senescence-associated secretory phenotype.