Statins demonstrate potential as multi-targeted adjuvant agents to reduce off-target gastrointestinal and cardiac toxicity during chemotherapy through pleiotropic protective mechanisms.
Do statins reduce chemotherapy-induced intestinal and cardiac toxicity?
Preclinical evidence suggests statins may be repurposed as multi-targeted adjuvant agents to reduce chemotherapy-induced cardiotoxicity and gastrointestinal toxicity, warranting further clinical studies.
Chemotherapy-induced gastrointestinal and cardiac toxicities remain major dose-limiting complications of several cancer treatments, often leading to long-term morbidity and reduced quality of life. Increasing attention has been given to the pleiotropic effects of statins, a class of 3-hydroxy-3-methylglutaryl coenzyme A-reductase inhibitors widely used for hyperlipidemia and cardiovascular risk reduction. Beyond their lipid-lowering properties, statins exhibit antioxidant, anti-inflammatory, anti-apoptotic, mitochondrial-protective, and endothelial-supportive activities, making them compelling candidates for repurposing in oncology. This review summarizes the molecular mechanisms through which statins may protect non-target tissues from the collateral damage of chemotherapy. We describe how statins attenuate oxidative stress via NADPH oxidase inhibition and enhancement of endogenous antioxidant defenses, and how they modulate inflammatory responses through suppression of NF-κB signaling and upregulation of endothelial nitric oxide synthase. We further describe their ability to reduce apoptosis by stabilizing mitochondria, activating pro-survival kinases, and dampening inflammasome activity. These effects are supported by preclinical evidence in models of doxorubicin-induced cardiotoxicity and intestinal mucositis. While clinical data remains limited and occasionally inconsistent, the mechanistic rationale and growing experimental data underscore the potential of statins as multi-targeted adjuvant agents to reduce off-target toxicity during chemotherapy. Future clinical studies are warranted to determine statin class-specific effects, optimal dosing, and their full therapeutic potential in cancer patients.
Arendt et al. (Thu,) conducted a review in Chemotherapy-induced gastrointestinal and cardiac toxicities. Statins was evaluated. Statins demonstrate potential as multi-targeted adjuvant agents to reduce off-target gastrointestinal and cardiac toxicity during chemotherapy through pleiotropic protective mechanisms.