Targeting the Mevalonate Pathway to Reduce Mortality from Ovarian Cancer
Abstract
The primary purpose was to evaluate whether statins, a well-known cholesterol-lowering agent, could 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 nonusers 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 2:a) assess the anti-tumor effect of lovastatin, (a commonly prescribed statin) alone or in combination with carboplatin/paclitaxel 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2017
- Accession Number
- AD1049942
Entities
People
- Kala Visvanathan
Organizations
- Johns Hopkins University