Steroid hormones have been implicated to play a fundamental role in the pathogenesis of prostate cancer. Polymorphisms in the genes that code for enzymes, or hormones involved in androgen regulatory pathway, reportedly influence risk for developing prostate cancer. Since many membrane transporters are modulators of steroid hormones absorption and tissue distribution, genetic polymorphisms in genes encoding these transporters may account for the risk of prostate cancer and the predicting of survival. The OATP1B3 (formerly OATP8) steroid uptake transporter is overexpressed in prostate cancer, and polymorphisms in SLCO1B3 were associated with altered testosterone uptake, and also an increased prostate cancer risk.
This invention identifies two polymorphic genetic markers in the SLCO1B3 (formerly SLC21A8) gene, called 334T>G and 699G>A, that can be measured in genomic DNA obtained from a blood sample to predict patient survival from a prostate cancer diagnosis. This genetic profiling result has profound clinical applications for diagnosis and treatment. Specifically, the inventors provided a correlation between clinical outcome of SLCOlB3 genotype with median survival of androgen-independent prostate cancer. They also showed that the genotype is predictive of testosterone uptake through the OATP1B3 transporter. This information is useful to inform clinical decisions regarding anti-androgen therapy.
• Cancer susceptibility testing represents one of the major assets in medical practice.
• SLCO1B3 genotyping can be used in combination on a gene chip with several polymorphisms known to predict survival of prostate cancer patients. Thus, the OATP1B3 polymorphism would be one genetic marker in a series of other markers that would be used to inform clinical decisions.
• SLCO1B3 upregulation can be used as a prognostic tool.
• Potential decrease in severity of side-effects due to ineffective chemotherapeutic agents.
• Potential improvement in design and selection of chemotherapeutic regimens.
• This invention provides a novel marker approach to predicting clinical outcomes in certain patients with prostate cancer.
• Analysis of the markers identified allow a clinician to make informed decisions for personalized cancer therapies.
• New marker for personalized medicine.
William Figg, Alex Sparreboom, Akinobu Hamada, Douglas K. Price, Tristan M. Sissung
- U.S. Patent Filed: U.S. Patent Application Number PCT/US2008/000310
- U.S. Patent Filed: U.S. Patent Application Number 60/879,503
- U.S. Patent Filed: U.S. Patent Application Number 12/522,480