Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer
Technical Report,30 Sep 2015,29 Sep 2016
Johns Hopkins University Baltimore United States
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The primary purpose is to evaluate whether statins, a well-known cholesterol-lowering agent, will improve survival in women with epithelial ovarian cancer. Aim 1 a prospectively examine whether statin use reduces both cancer specific and overall mortality among approximately 7886 women with epithelial ovarian cancer after adjustment for stage, grade, treatment, histologic subtype, co-medication use, type of surgery and type of hospital. Statin use will be compared to non-users as well as users of other lipid lowering agents and b test whether the association is modified by i dose and duration, ii timing of the intervention pre-diagnosis versus post diagnosis use, iii histologic subtype and iv degree of adherence. Aim 2a assess the anti-tumor effect of lovastatin, a commonly prescribed statin alone or in combination with carboplatinpaclitaxel in a mouse orthotopic tumor xenograft model bearing luciferase-expressing OVCAR3, SKOV3, and A2780 cells and b determine the molecular mechanism by which lovastatin inhibits tumor growth. The clinical and translational impact of this project are substantial because unlike other potential new drug treatments, statins are already in wide use, have been shown to have very low toxicity and could therefore be put quickly into practice if clinical trials confirm their efficacy and at low cost.
- Medicine and Medical Research