This review investigates how radiation therapy (RT) increases the risk of delayed cardiovascular disease (CVD) in cancer survivors. Understanding the mechanisms underlying radiation-induced CVD is essential for developing targeted therapies to mitigate these effects and improve long-term outcomes for patients with cancer.
Recent Advances:
Recent studies have primarily focused on metabolic alterations induced by irradiation in various cancer cell types. However, there remains a significant knowledge gap regarding the role of chronic metabolic alterations in normal cells, particularly vascular cells, in the progression of CVD after RT.
Critical Issues:
This review centers on RT-induced metabolic alterations in vascular cells and their contribution to senescence accumulation and chronic inflammation across the vasculature post-RT. We discuss key metabolic pathways, including glycolysis, the tricarboxylic acid cycle, lipid metabolism, glutamine metabolism, and redox metabolism (nicotinamide adenine dinucleotide/Nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADP+)/NADPH). We further explore the roles of regulatory proteins such as p53, adenosine monophosphate-activated protein kinase, and mammalian target of rapamycin in driving these metabolic dysregulations. The review emphasizes the impact of immune-vascular crosstalk mediated by the senescence-associated secretory phenotype, which perpetuates metabolic dysfunction, enhances chronic inflammation, drives senescence accumulation, and causes vascular damage, ultimately contributing to cardiovascular pathogenesis.
Future Directions:
Future research should prioritize identifying therapeutic targets within these metabolic pathways or the immune-vascular interactions influenced by RT. Correcting metabolic dysfunction and reducing chronic inflammation through targeted therapies could significantly improve cardiovascular outcomes in cancer survivors. Antioxid. Redox Signal. 43, 92–114.
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