Validating Biomarkers for Use in Predicting Abiraterone Resistance in Prostate Cancer

Abstract

By Chloe Boehmer, Biochemistry & Women's, Gender, and Sexuality Studies; Dan Song, University of Cincinnati; Pheruza Tarapore, Univerity of Cincinnati

Advisor: David Smithrud

Awards: Capstone Competition: Second Place Winner

Presentation ID: 33

Abstract: Prostate cancer (PCa) is the second most common cancer diagnosed in American men. Progression of PCa during the early stages is dependent on androgen. First-line treatments consequently rely on inhibiting the functioning of the androgen receptor. However, resistance develops giving rise to hormone/castration-resistant prostate cancer (CRPC). This cancer is typically treated with second generation anti-androgens such as abiraterone (Abi), which targets the steroidogenic enzyme CYP17A1. Some tumors do not respond to Abi, however, and some of those which do respond eventually become Abi-resistant (Abi-R). Identification of markers predicting Abi-R is essential for precision medicine. Using a patient-derived xenograft (PDX) mouse model which mimics the development of Abi-R, previous work identified differentially expressed genes to distinguish between Abi-R and either CRPC or Abi-sensitive (Abi-S) tumors. The current project is focused on validating these genes through quantitative real-time PCR (qPCR). We used NIH Primer-BLAST software to identify primer sequences to be used in qPCR. Primers were designed for genes that predict Abi-R and first tested for their utility through qPCR. We varied the temperature and time of annealing to increase primer-pair specificity. The melt curve of products was used as a readout for specificity. Agarose gel electrophoresis was performed to confirm size of generated product. So far, we have identified primers specific for 15 genes. We are now ready to validate our biomarker signature for resistance in our PDX mouse model and in human samples.