Molecular and cellular crosstalk between atherosclerosis and cancer: Mechanistic insights and therapeutic opportunities.

Abstract

Atherosclerosis and cancer are among the leading causes of morbidity and mortality worldwide and are increasingly recognized as biologically interconnected diseases rather than independent pathological conditions. Accumulating evidence indicates that these disorders share a complex molecular landscape characterized by chronic inflammation, oxidative stress, immune dysregulation, metabolic reprogramming, endothelial dysfunction, and age-related cellular alterations. This review integrates current knowledge on the molecular and cellular mechanisms underlying the bidirectional relationship between atherosclerosis and malignancy, with particular emphasis on inflammatory signaling pathways, NLRP3 inflammasome activation, macrophage polarization, clonal hematopoiesis of indeterminate potential (CHIP), cellular senescence, and gut microbiota-mediated immune modulation. We further discuss how these shared mechanisms contribute to disease initiation, progression, and therapeutic responses, highlighting the influence of cardiovascular medications on cancer biology and the cardiovascular toxicities associated with anticancer therapies. By synthesizing emerging evidence from cardiovascular biology, oncology, and immunology, this review proposes a unified molecular framework in which atherosclerosis and cancer represent interconnected manifestations of common pathogenic processes. Recognizing this molecular crosstalk provides new opportunities for the identification of shared biomarkers, improved risk stratification, and the development of mechanism-based therapeutic strategies, thereby advancing precision medicine at the interface of cardiovascular disease and cancer.