SUO 2016: SLCO2B1: Biology & Therapeutic Implications - Session Highlights
San Antonio, Texas USA (UroToday.com) Dr. Harshman presented original research that studied the influence and manipulation of the SLCO2B1 transporter in prostate cancer treatment. SLCO2B1 is a gene that encodes a sodium-independent organic anionic transporter that is responsible for mediating the transport of a variety of hormones and drugs into cells.
Studies have shown that expression of SLCO2B1 increases with progression from hormone-sensitive to castration-resistant prostate cancer. Interestingly, sophisticated gene analysis has demonstrated that this transporter is an important mediator of androgen metabolism. Higher risk SLCO2B1 alleles are associated with shorter prostate cancer survival, so understanding the functional role of this transporter is paramount.
An important molecule that is transported is DHEAS (responsible for androgen entry into cells). Statins are a commonly used drug that also experience uptake with the SLCO2B1 transporter. Dr. Harshman presented retrospective data suggesting that statin use has an inverse relationship with prostate cancer incidence and mortality – statin use appears to be beneficial in both of these outcomes. Investigators demonstrated that statins compete against and inhibit DHEAS uptake within tumor cells, and that this effect is concentration-dependent and similar across multiple statin medications. They therefore hypothesized that statin use at the time of ADT initiation would improve prostate cancer outcomes, such as time to progression (TTP). In a study of 1265 patients, they found that statin users at ADT initiation did indeed have a significantly longer 10-month median TTP on ADT: 27.5 vs. 17.4 months (p=0.0005).
Abiraterone is a steroidal drug that could also be influenced SLCO-mediated transport, and work by Dr. Xiaodong Wang found that uptake of abiraterone is indeed SLCO dependent. Dr. Harshman and colleagues predicted that statins may INHIBIT the effectiveness of abiraterone by competing for cellular uptake via SLCO transporters. Interestingly though, a retrospective analysis of 224 patients over 7 years found that in the 41% of patients taking statins, there was an opposite effect: There was a trend toward longer abiraterone duration in statin users. This would suggest that statins do not have a negative impact on abiraterone effectiveness. However, a subsequent analysis using patients in the Hopkins database that had more advanced disease did not show a significant signal.
As Dr. Harsman concludes, there is evidence that statins compete with DHEAS for uptake into tumor cells by SLCO2B1, which may decrease the tumor’s available androgen pool. This may translate into improved outcomes for patients initiating ADT who use statins. Although it was feared that statin use may inhibit the effectiveness of abiraterone, research suggests that statin use does not appear to have a negative impact. Clearly, further prospective studies will help delineate the complete nature of these associations.
Presented By: Lauren Harshman, MD, Dana-Farber Cancer Institute
Written By: Shreyas Joshi, MD, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA