Use of Fenofibrate in the Management of Protease Inhibitor‐Associated Lipid Abnormalities

Thomas, James C.; Lopes‐Virella, Maria F.; Bene, Victor E. Del; Cerveny, Joli D.; Taylor, Kelly B; McWhorter, Laura Shane; Bultemeier, Nanette C.

doi:10.1592/phco.20.7.727.35179

Cited by 51 publications

(35 citation statements)

References 33 publications

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“…We have postulated nelfinavir as a complementary off target treatment for cancer 143 . The association of FF with nelfinavir may prevent lipodystrophy, hypertriglyceridemia and elevation of lipoparticules [144][145][146] . There is no experimental proof of synergy of this interaction regarding cancer treatment, but both drugs share certain characteristics that make synergy a very plausible feature.…”

Section: Yang Cs 2013mentioning

confidence: 99%

Fenofibrate in cancer: mechanisms involved in anticancer activity

Koltai¹

2015

F1000Res

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Discuss this article AbstractTo review the mechanisms of anti-cancer activity of fenofibrate (FF) Objective: and other Peroxisome Proliferator Activator Receptor α (PPARα) agonists based on evidences reported in the published literature.We extensively reviewed the literature concerning FF as an off target Methods: anti-cancer drug. Controversies regarding conflicting findings were also addressed.The main mechanism involved in anti-cancer activity is Results: anti-angiogenesis through down-regulation of Vascular Endothelial Growth Factor (VEGF), Vascular Endothelial Growth Factor Receptor (VEGFR) and Hypoxia Inducible factor-1 α (HIF-1α), inhibition of endothelial cell migration, up-regulation of endostatin and thrombospondin-1, but there are many other contributing mechanisms like apoptosis and cell cycle arrest, down-regulation of Nuclear Factor Kappa B (NF-kB) and Protein kinase B (Akt) and decrease of cellular energy by impairing mitochondrial function. Growth impairment is related to down-regulation of Phospho-Inositol 3 Kinase (PI3K)/Akt axis and down-regulation of the p38 map kinase (MAPK) cascade. A possible role should be assigned to FF stimulated over-expression of Tribbles Homolog-3 (TRIB3) which inhibits Akt phosphorylation. Important anti-cancer and anti-metastatic activities are due to down-regulation of MCP-1 (monocyte chemotactic protein-1), decreased Metalloprotease-9 (MMP-9) production, weak down-regulation of adhesion molecules like E selectin, intercellular adhesion molecules (ICAM) and Vascular Endothelial Adhesion Molecules (VCAM), and decreased secretion of chemokines like Interleukin-6 (IL-6), and down-regulation of cyclin D-1. There is no direct link between FF activity in lipid metabolism and anticancer activity, except for the fact that many anticancer actions are dependent from PPARα agonism. FF exhibits also PPARα independent anti-cancer activities.There are strong evidences indicating that FF can disrupt Conclusions: growth-related activities in many different cancers, due to anti-angiogenesis and anti-inflammatory effects. Therefore FF may be useful as a complementary adjunct treatment of cancer, particularly included in anti-angiogenic protocols like those currently increasingly used in glioblastoma. There are sound reasons to initiate well planned phase II clinical trials for FF as a complementary adjunct treatment of cancer.

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Section: Yang Cs 2013mentioning

confidence: 99%

Fenofibrate in cancer: mechanisms involved in anticancer activity

Koltai¹

2015

F1000Res

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“…Nonpharmacologic approaches involve therapeutic lifestyle changes, such as increased exercise and dietary changes. [44][45][46] A number of diverse agents, such as interferon, 47 olanzapine, 48 propofol, 49 and human immunodeficiency virus protease inhibitors, 50 have the potential to promote hypertriglyceridemia; therefore, removal and replacement of these agents should be considered in therapeutic planning. Statins have only modest effects on lowering TG and raising HDL-C levels; thus, in treating mixed dyslipidemia, the addition of fibrates, niacin, or P-OM3 is often required to bring TGs and concluded about the superiority of either therapy.…”

Section: Combination Therapy For Mixed Dyslipidemiamentioning

confidence: 99%

Maintaining Cardiovascular Health in Patients With Mixed Dyslipidemia Optimizing the Management of Hypertriglyceridemia and Non-HDL Cholesterol

Ito¹,

McKenney²,

Brinton³

2009

JMCP

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“…Several studies of the use of fenofibrate in the management of the hyperlipidemia of highly-active antiretroviral therapy (HAART) (specifically with protease inhibitors) have been published recently (8,15,64).…”

Section: Table 3 (Continued)mentioning

confidence: 99%

Update on Fenofibrate

Guay

2002

Cardiovascular Drug Reviews

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Fenofibrate is a fibric acid derivative that has been marketed since the mid-1970's (1998 in the United States). Its active metabolite, fenofibric acid, is responsible for the primary pharmacodynamic effects of the drug: reductions in total plasma cholesterol, lowdensity lipoprotein cholesterol, triglycerides, and very low-density lipoprotein concentrations and increases in high-density lipoprotein cholesterol and apolipoproteins AI and AII concentrations. These effects are mediated by activation of peroxisome proliferator-activated receptor-á (PPAR á ). The drug has broad spectrum utility, with documented efficacy in Fredrickson types IIa, IIb, III, IV, and V hyperlipidemias. Fenofibrate is well tolerated, with digestive and musculoskeletal side effects similar to those of other fibrates. Results of the initial cardiovascular morbidity/mortality outcomes study with fenofibrate (known as DAIS [Diabetes Atherosclerosis Intervention Study]) were encouraging vis-à-vis slowing of atherosclerotic progression in the coronary vasculature of type II diabetics. The results of other ongoing outcome trials are eagerly awaited. These results will help to establish the overall place of fenofibrate in the hypolipidemic armamentarium.

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Use of Fenofibrate in the Management of Protease Inhibitor‐Associated Lipid Abnormalities

Cited by 51 publications

References 33 publications

Fenofibrate in cancer: mechanisms involved in anticancer activity

Fenofibrate in cancer: mechanisms involved in anticancer activity

Maintaining Cardiovascular Health in Patients With Mixed Dyslipidemia Optimizing the Management of Hypertriglyceridemia and Non-HDL Cholesterol

Update on Fenofibrate

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