The use of cholesterol-lowering statins when men initiated androgen deprivation therapy for prostate cancer was associated with longer time to progression of the disease.
The gene SLCO2B1 acts as a transporter that enables a variety of drugs and hormones to enter cells. For example, dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and uses SLCO2B1 to get into cells. Similarly, statins use SLCO2B1 to enter cells as well. Previous research has suggested an association between statin use and improved clinical outcomes for prostate cancer. But little is known about the impact of statin use and response to androgen deprivation therapy (ADT), the cornerstone of treatment for metastatic hormone-sensitive prostate cancer, according to the study background.
Conceivably, statins might interfere with the ability of DHEAS to get into cells and thus delay resistance to ADT by this mechanism.
Dr Philip W Kantoff, of the Dana-Farber Cancer Institute, Boston, and co-authors examined statin use and time to progression of disease during ADT for prostate cancer. The authors conducted in vitro studies on prostate cancer cell lines to examine whether statins interfered with DHEAS uptake. Statin use was analysed in 926 patients who had ADT for prostate cancer between 1996 and 2013. The authors found in the in vitro studies that statins block DHEAS uptake by competitively binding to SLCO2B1.
Of the 926 patients in the study, 283 (31%) were taking a statin when they started ADT. After a median follow-up of nearly six years, 644 patients (70%) experienced disease progression while receiving ADT. The overall median time to progression was 20.3 months but men taking statins had a longer median time to progression during ADT compared with nonusers (27.5 months vs. 17.4 months), according to the study.
"Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intra-tumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP (time to progression) in statin users," the article concludes.
[link url="http://media.jamanetwork.com/news-item/statins-associated-with-longer-prostate-cancer-time-to-progression-during-androgen-deprivation-therapy/"]JAMA material[/link]
[link url="http://oncology.jamanetwork.com/article.aspx?articleid=2288665"]JAMA Oncology abstract[/link]
[link url="http://oncology.jamanetwork.com/article.aspx?articleid=2288662"]JAMA Oncology editorial[/link]