Precision detection would “focus on a patient’s individual variant androgen receptor burden.”
Previously in Discovery, we reported an important breakthrough in understanding why two second-line hormonal therapy drugs for metastatic castration-resistant prostate cancer (CRPC) don’t help some men. The drugs, enzalutamide (Xtandi) and abiraterone (Zytiga) are very expensive, and if they are not going to work, men can save thousands of dollars a month – and better yet, try something different that may prove more successful. Both drugs target the androgen receptor, but like a key trying to fit the wrong lock, the drugs fail to work in men who develop a mutated androgen receptor. Brady scientists Jun Luo, Ph.D., and Emmanuel Antonarakis, M.D., not only discovered this variant receptor, called AR-V7; they developed a blood test for it.
Now, they would like to refine their test even further to offer “precision detection,” says Luo, “to focus on a patient’s individual variant androgen receptor burden.” To do this, in tissue studies conducted by Brady pathologist Angelo De Marzo, M.D., Ph.D., they are using a novel RNA in situ hybridization (RISH) method they developed “to visualize AR-V7, achieving a resolution of a single splice junction.” Basically, this means that they can look for variant receptors on the molecular level – one molecule at a time – “to determine a patient’s overall variant androgen receptor burden beyond AR-V7.” A study using their new technology was recently published in European Urology. Postdoctoral fellow Yezi Zhu, Ph.D., is a co-investigator on this project.”