Cholesterol metabolism and cancer: Molecular mechanisms, immune regulation and an epidemiological perspective (Review)

Abstract

cholesterol and its metabolites exert multifaceted and profound effects on cancer initiation, progression and therapeutic response as well as patient prognosis. The present review systematically summarizes the oncogenic role of cholesterol metabolism in malignancies. cancer cells exten‑ sively remodel cholesterol homeostasis through enhanced synthesis, increased uptake and impaired efflux, thereby sustaining proliferative signaling, suppressing ferroptotic cell death, promoting autophagic survival and facilitating epithelial‑mesenchymal transition, collectively fueling tumor invasion and metastasis. Within the tumor immune microenvi‑ ronment, cholesterol exhibits dual immunoregulatory roles; it potentiates T‑cell antitumor function while its oxidized deriva‑ tives contribute to T‑cell exhaustion. Therapeutic targeting of cholesterol metabolism represents a promising strategy to trigger ferroptosis, reverse chemoresistance and reinvigorate antitumor immunity. Nevertheless, epidemiological evidence regarding the correlation between cholesterol levels and cancer risk remains contentious, underscoring the context‑dependent and complex nature of cholesterol in oncology. Targeting cholesterol metabolism may thus offer a novel integrative approach for cancer therapy, meriting further mechanistic and clinical investigation.