Accession Number:

AD1004097

Title:

SLCO2B1 and SLCO1B3 as New Targets for Enhancing Androgen Deprivation Therapy for Prostate Cancer

Descriptive Note:

Technical Report,30 Sep 2014,29 Sep 2015

Corporate Author:

Dana-Farber Cancer Institute Boston United States

Personal Author(s):

• Kantoff,Philip

Report Date:

2015-10-01

Pagination or Media Count:

85.0

Abstract:

We found the association between the SLCO2B1 exonic SNP rs12422149 and time to progressionTTP on ADT. We also found that the intronic SNP rs1077858 was associated with overall survival. SLCO2B1 expression in normal prostate tissue and in 22RV1 cells carrying the major allele of SNP rs1077858 was significantly lower than those carrying the risk allele. In vitro, we showed SLCO2B1 expression levels correlated with DHEAS uptake by PC cells. Our data shown that statin use at the time of ADT initiation was associated with a significantly longer TTP on ADT even after adjusting for known prognostic factors. Our in vitro findings that statins competitively reduce DHEAS uptake and thus, effectively decrease the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.

Descriptors:

• prostate cancer
• androgens
• therapy
• RECEPTOR SITES(PHYSIOLOGY)
• neoplasms
• estrogens
• metabolism
• hormones
• CHEMOTHERAPY

Subject Categories:

Distribution Statement:

APPROVED FOR PUBLIC RELEASE