Statins and pancreatic cancer (Review)

Gong,Jun; Sachdev,Esha; Robbins,Lori  A.; Lin,Emily; Hendifar,Andrew  E.; Mita,Monica   M.

doi:10.3892/ol.2017.5572

Statins and pancreatic cancer (Review)

Authors:
- Jun Gong
- Esha Sachdev
- Lori A. Robbins
- Emily Lin
- Andrew E. Hendifar
- Monica M. Mita
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Affiliations: Department of Medical Oncology, City of Hope National Medical Center, Duarte, CA 91010, USA, Department of Internal Medicine, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA, Department of Internal Medicine, Harbor‑UCLA Medical Center, Torrance, CA 90509, USA, Department of Internal Medicine, Division of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA, Experimental Therapeutics Program, Samuel Oschin Comprehensive Cancer Institute, Cedars‑Sinai Medical Center, Los Angeles, CA 90048, USA
Published online on: January 4, 2017 https://doi.org/10.3892/ol.2017.5572
Pages: 1035-1040

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Abstract

Pancreatic cancer remains among the most lethal cancers, despite ongoing advances in treatment for all stages of the disease. Disease prevention represents another opportunity to improve patient outcome, with metabolic syndrome and its components, such as diabetes, obesity and dyslipidemia, having been recognized as modifiable risk factors for pancreatic cancer. In addition, statins have been shown to potentially reduce pancreatic cancer risk and to improve survival in patients with a combination of metabolic syndrome and pancreatic cancer. Furthermore, preclinical studies have demonstrated that statins exhibit antitumor effects in pancreatic cancer cell lines in vitro and animal models in vivo, in addition to delaying the progression of pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma (PDAC) and inhibiting PDAC formation in conditional K‑Ras mutant mice. The mechanisms by which statins produce anticancer effects remain poorly understood, although appear to involve inhibition of the mevalonate/cholesterol synthesis pathway, thus blocking the synthesis of intermediates important for prenylation and activation of the Ras/mitogen‑activated protein kinase 1 signaling pathway. Furthermore, statins have been identified to modulate the phosphoinositide 3‑kinase/Akt serine/threonine kinase 1 and inflammation signaling pathways, and to alter the expression of genes involved in lipid metabolism, which are important for PDAC growth and proliferation. In addition, statins have been demonstrated to exhibit further antitumor mechanisms in a number of other cancer types, which are beyond the scope of the present review. In the present review, current evidence highlighting the potential of statins as chemopreventive agents in pancreatic cancer is presented, and the antitumor mechanisms of statins elucidated thus far in this disease are discussed.

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