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Ezetimibe and Cancer: Is There a Connection?

ABSTRACT: The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.

SUBMITTER: Gu J

PROVIDER: S-EPMC9340271 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Ezetimibe and Cancer: Is There a Connection?

Gu Jia J Zhu Neng N Li Hong-Fang HF Zhang Chan-Juan CJ Gong Yong-Zhen YZ Liao Duan-Fang DF Qin Li L

Frontiers in pharmacology 20220718

The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have show ...[more]

PMID: 35924044

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Project description:To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.This review is based on a systematic literature search (1995 to July 2015) in PubMed, the Excerpta Medica Database (EMBASE), the Cochrane Library, and the ClinicalTrials.gov registry.Nine randomized, controlled trials with data from a total of 19 461 patients were included. Ezetimibe-statin combination therapy was associated with a lower risk of cardiovascular events than statin monotherapy: 33% of the patients treated with ezetimibe and a statin, and 35% of those treated with a statin alone, had a cardiovascular event within seven years (number needed to treat [NNT]: 50 over 7 years). Combination therapy was also significantly more effective in preventing a composite endpoint consisting of death due to cardiovascular disease, nonfatal myocardial infarction, unstable angina pectoris, coronary revascularization, and nonfatal stroke (hazard ratio [HR] 0.94, 95% confidence interval [0,89; 0,99]; p = 0.016). Diabetic patients benefited from combination therapy rather than monotherapy with respect to cardiovascular morbidity (HR 0.87 [0.78; 0.94]). On the other hand, the addition of ezetimibe to statin therapy did not lessen either cardiovascular or overall mortality. Serious undesired events occurred in 38% of the patients taking ezetimibe and a statin nd in 39% of the patients taking a statin alone (relative risk 1.09 [0.77; 1.55]).In high-risk patients with an acute coronary syndrome, combination therapy with ezetimibe and a statin lowered the risk of cardiovascular events in comparison to statin monotherapy. The risk of dying or suffering an adverse drug effect was similar in the two treatment groups.

Project description:Ovarian cancer is most lethal among gynecological cancers with often fatal consequences due to lack of effective biomarkers and relapse, which propels ovarian cancer research into unique directions to establish solid targeted therapeutics. "Ovarian stem cells" expressing germline pluripotent markers serve as novel paradigm with potential to address infertility, menopause, and probably influence tumor initiation. Cancer stem cells (CSCs) pose vital role in tumor recurrence and hence it is extremely important to study them with respect to ovarian stem cells across various cancer stages and normal ovaries. Pluripotent (OCT4, NANOG, SOX2, SSEA1, and SSEA4), germline (IFITM3, VASA/DDX4), and cancer stem (CD44, LGR5) cell specific markers were characterized for protein and mRNA expression in tumor tissues to understand their distribution in the surface epithelium and ovarian cortex in benign, borderline, and high-grade malignant stages. To elucidate whether pluripotent ovarian germline stem cells and CSCs are common subset of stem cells in tumor tissues, VASA was colocalized with known pluripotent stem (OCT4, SSEA1, SSEA4) and CSC (CD44, LGR5) specific markers by confocal microscopy. Single, smaller spherical (≤5 μm), and larger elliptical fibroblast like (≥10 μm) cells (also in clusters or multiples) were detected implying probable functional behavioral significance of cells in tumor initiation and metastasis across various cancer stages. Cells revealed characteristic staining pattern in ovarian surface epithelium (OSE) and cortex regions exclusive for each marker. Co-expression studies revealed specific subpopulations existing simultaneously in OSE and cortex and that a dynamic hierarchy of (cancer) stem cells with germline properties prevails in normal ovaries and cancer stages. Novel insights into CSC biology with respect to ovarian and germline stem cell perspective were obtained. Understanding molecular signatures and distribution within ovarian tissue may enable identification of precise tumor-initiating CSC populations and signaling pathways thus improving their efficient targeting and strategies to prevent their dissemination causing fatal relapse.

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Ezetimibe and Cancer: Is There a Connection?

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Ezetimibe and Cancer: Is There a Connection?

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