NEW YORK (Reuters Health) - Statin users with hormone-sensitive prostate cancer have significantly longer time to progression than nonusers do, likely due to reduced dehydroepiandrosterone sulfate (DHEAS) uptake, researchers say.
Statin use has previously been linked to better prostate cancer outcomes.
Dr. Philip W. Kantoff from Dana-Farber Cancer Institute, Boston, and colleagues showed recently that genetic variants of SLCO2B1, an organic transporter used by statins and DHEAS to enter cells, correlated with time to progression (TTP) during receipt of androgen deprivation therapy (ADT) for prostate cancer.
In the current study, Dr. Kantoff's team looked for interactions between statins and DHEAS influx by SLCO2B1 in prostate cancer cell lines and used their institutional clinical database to evaluate the association between statin use and TTP among 926 men (283 taking statins) with prostate cancer who were receiving ADT.
All four statins they examined (atorvastatin, fluvastatin, pravastatin, and simvastatin) competed with DHEAS for the SLCO2B1 transporter, and knocking down SLCO2B1 abolished inhibition of DHEAS uptake.
In androgen-dependent prostate cancer cell lines, atorvastatin efficiently blocked SLCO2B1-mediated DHEAS uptake and DHEAS-induced cell growth, according to the May 7 JAMA Oncology online report.
Median TTP among the statin users was 27.5 months, significantly longer than the 17.4 months among nonusers (p<0 .001="" 17="" a="" adjustment="" after="" associated="" even="" factors="" for="" in="" of="" other="" p="" progression.="" reduction="" relative="" risk="" statin="" the="" use="" was="" with="">
"The mechanism through which statins exert their activity in prostate cancer is likely multifactorial, including antiproliferative and proapoptotic effects," the researchers explained. "However, the most plausible mechanism is the reduction in the tumor's androgen stores through a combination of decreased availability of the cholesterol precursor required for de novo synthesis and decreased transport of existing precursor androgens such as DHEAS via competitive binding of SLCO2B1."
"Ultimately, these results require prospective validation," they concluded. "More than 10 prospective trials are ongoing or maturing that will further characterize the role of statins as anticancer therapies in prostate cancer."
Dr. Jorge D. Ramos and Dr. Evan Y. Yu from University of Washington School of Medicine, Seattle, Washington wrote an accompanying editorial. Dr. Ramos told Reuters Health by email, "There have been several retrospective studies that have suggested that statins may help prevent the development of cancer or the progression of cancer in those already diagnosed. The difference in this study is that the authors provided a strong, plausible mechanism on how statins may improve outcomes in patients that have prostate cancer, which has not been done before in prostate cancer."
"Statins may have a role in the treatment of prostate cancer, but there is not enough evidence to support putting patients on statins for this purpose at this time," Dr. Ramos concluded. "Statins need to be studied in a prospective manner with clinical trials."
Dr. Laurent Azoulay, oncologist and prostate cancer expert from McGill University, Montreal, Quebec, Canada, agreed. He told Reuters Health by email, "There is a convergence of data suggesting that statins may be beneficial in patients with prostate cancer. However, until trials are conducted in this population, this treatment should be reserved to those who need them for primary and secondary cardiovascular prevention."
The Dana-Farber Cancer Institute Special Programs of Research Excellence and the Department of Defense funded this research. Dr. Kantoff reported serving as vice president, Apple Tree Partners, an investor in Tokai Pharmaceuticals, which is developing prostate cancer therapies.
SOURCE: http://bit.ly/1F5QSPR and http://bit.ly/1zYpQtx
JAMA Oncol 2015.
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