Statins and the Lipidome in Prostate Cancer
Research impact: Drugs currently used to reduce cholesterol may serve to target abnormal fat metabolism in prostate cancer that is associated with worse outcomes
Previous research and rationale
In men with prostate cancer, we have identified particular patterns of lipid (fat/cholesterol) species in blood. This is referred to as the “lipidome signature”, and we have also found that different signatures are associated with a better or worse cancer prognosis. Preliminary evidence from our researcrch also suggests that these lipid signatures reflect changes in the normal lipid metabolism within prostate cancer cells.
Statins are a class of drug commonly prescribed to reduce blood fat-cholesterol levels. Our research to date indicates that the lipids in the lipidome signature of men with a poor prostate cancer prognosis may be responsive to treatment with statins.
Hypothesis
We therefore hypothesise that treatment of men with prostate cancer with statins may reduce levels of the lipids in the lipidome signature associated with worsening of disease, and therefore improve outcomes.
Aim
We are undertaking a clinical study is to assess whether co-treatment of men with the statin Simvastatin during treatment for metastatic prostate cancer can reverse a poor prognostic plasma lipididome signature.
Our study
Men who are being treated with metastatic prostate cancer are being treated with simvastatin 40mg daily (oral tablet) for 12 weeks, at the same time as starting chemotherapy (docetaxel or cabazitaxel) or anti-androgen treatment (abiraterone or enzalutamide). The blood lipidome signature is being recorded at baseline and at the end of treatment and the signature will be compared to the outcomes of treatment in men.
More information about this clinical trial may be found at:
ANZ Clinical Trials Register Study ID: ACTRN12617000965303 (NSW Study)
Contact: Professor Lisa Butler
FCMHW@The University of Adelaide & South Australian Health & Medical Research Institute
References from the Centre
Butler LM et al. Lipidomic profiling of clinical prostate cancer reveals targetable alterations in membrane lipid composition. Cancer Res. 2021 Aug 6:canres.3863.2020. doi: 10.1158/0008-5472.CAN-20-3863. Epub ahead of print. PMID: 34362796
Centenera MM et al. ELOVL5 Is a Critical and Targetable Fatty Acid Elongase in Prostate Cancer. Cancer Res. 2021 Apr 1;81(7):1704-1718. doi: 10.1158/0008-5472.CAN-20-2511. Epub 2021 Feb 5. PMID: 33547161.
Grossmann M & Wittert G. Androgens, diabetes and prostate cancer. Endocr Relat Cancer. 2012 Sep 5;19(5):F47-62. doi: 10.1530/ERC-12-0067. PMID: 22514110.