SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer
Technical Report,30 Sep 2015,29 Sep 2016
Dana-Farber Cancer Institute Boston United States
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We found and validated that the SLCO2B1 exonic SNP rs12422149 was significantly associated with time to progression TTP on ADT and that the intronic SNP rs1077858 was associated with overall survival in prostate cancer. The SLCO2B1 exonic SNP rs12422149 significantly impacts the efficiency of the transporter. Individuals or cell lines carrying the major allele of SNP rs1077858 have a significantly lower level of SLCO2B1 expression, compared to those carrying the minor risk allele. SLCO2B1 expression levels are directly correlated with DHEAS uptake in prostate cancer cell lines. Additional studies showed that statin use at the time of ADT initiation was associated with a significantly longer TTP on ADT even after adjusting for known clinical prognostic factors. Our in vitro findings that statins competitively reduce DHEAS uptake and thus, effectively decrease the available intratumoral androgen, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.
- Medicine and Medical Research