Molecular mechanism behind the Beneficial Effects of Statins in Ovarian Cancer

Mauricio A. Cuello; Sumie Kato; Lorena Abarzúa-Catalán; Eric R. Travers

Keywords: ovarian cancer, statin


Worldwide, epithelial ovarian cancer constitutes the most lethal gynecological malignancy. Annually, about 240.000 women are newly diagnosed and 150.000 die of this disease. Its lethality is mainly explained by a late diagnosis, at advanced stages, and by a transient response to available therapies. Thus, despite optimal surgical cytoreduction and a complete response to platinum-based chemotherapy, the majority of cases eventually relapses and dies of their disease determining a 5-year survival not exceeding 40%. Current hypothesis for ovarian carcinogenesis establishes as a major determinant for malignant transformation of ovarian surface epithelium the chronic exposure to an inflammatory environment. Several conditions predispose to chronic inflammation, one of them the obesity. More importantly, recent studies confer a prognosis even worse to those ovarian cancer patients that are obese. A possible explanation for a more deleterious outcome in this subpopulation can be found in the presence of metabolic abnormalities and higher levels circulating of pro-inflammatory mediators. In fact, studies by our group and others show that alterations in lipid metabolism and the presence of higher levels of leptin, both conditions commonly found in the obese population, favor a pro-inflammatory environment that promotes cell growth, invasion, metastasis, and resistance to chemotherapeutic agents by the cancer cells. Interestingly, some retrospective evidence suggests that patients receiving statins during their ovarian cancer treatment experience a better outcome than those not receiving them. Statins, HMGCoA reductase inhibitors, are usually prescribed to reduce cholesterol levels but they also possess pleiotropic effects that negatively influence ovarian carcinogenesis. By inhibiting the mevalonate pathway, statins would have a systemic effect, similar to that observed in atherosclerosis, reducing the inflammatory stimuli present in the tumor microenvironment and inhibiting the activation of multiple intracellular signaling cascades critical for metabolism, proliferation, cell death, migration, invasion, metastasis, and drug sensitivity of the ovarian cancer cell. In the present chapter we summarize the current evidence on molecular mechanisms supporting the beneficial effect of statins in ovarian cancer. In particular, reasons to maintain statin use among those newly diagnosed ovarian cancer patients already taking this medication. Furthermore, reasons to consider this drug in the design of future clinical trials in the treatment of epithelial ovarian cancer..

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Editorial: Nova Science Publishers, Inc.
Fecha de publicación: 2015
Página de inicio: 165
Página final: 182
Idioma: English