Cholesterol metabolism is central to cancer biology, influencing tumour initiation, progression, and therapeutic response, while contributing to the increased cardiovascular risk observed in cancer patients. Epidemiological studies investigating the relationship between circulating cholesterol levels and cancer risk have yielded conflicting results, reflecting substantial biological heterogeneity, tumour-specific metabolic demands, and methodological biases such as reverse causality. At the cellular level, malignant cells exhibit elevated cholesterol uptake and synthesis to sustain membrane biogenesis, lipid raft-dependent oncogenic signalling, and rapid proliferation. Cholesterol and its oxidized derivatives further modulate inflammation, angiogenesis, immune evasion, and key signalling pathways. Anticancer therapies profoundly disrupt lipid homeostasis; conventional chemotherapies, targeted therapies, hormone-modulating agents, and immunotherapies can induce dyslipidaemia and accelerate atherosclerotic disease, thereby contributing to long-term morbidity in cancer survivors. Conversely, lipid-lowering therapies—particularly statins—have emerged as pivotal tools in cardio-oncology, primarily for cardiovascular protection. Beyond this role, growing evidence suggests potential adjunctive antitumor effects mediated through inhibition of the mevalonate pathway, blockade of oncogenic signalling, and modulation of the tumour microenvironment. Novel agents, including ezetimibe, bempedoic acid, and proprotein convertase subtilisin-kexin type 9 inhibitors, provide additional therapeutic options, with emerging evidence supporting their immunomodulatory and anticancer properties, especially in combination with immune checkpoint inhibitors. Cholesterol metabolism plays a critical role in both CV disease and cancer biology, with growing evidence suggesting a complex bidirectional relationship between lipid homeostasis and tumour development. In addition, several anticancer therapies may profoundly affect lipid metabolism, thereby contributing to CV risk in cancer patients. The aim of this review is to provide a comprehensive overview of the interplay between cholesterol metabolism and cancer, to summarize the lipid-modifying effects of anticancer therapies, and to discuss the potential role of lipid-lowering strategies within the evolving framework of cardio-oncology care.
Piscione et al. (Thu,) studied this question.