If only prostate cancer could talk. Then we might be able to get direct answers to questions, such as: Is it still responding to treatment? Or: Has something important changed? Getting frequent updates from a biopsy is not feasible; it’s hard on the patient, and also an expensive, impractical way to search for answers. Last year in Discovery, we reported that Brady scientist Paula Hurley, Ph.D., and colleagues were getting close to finding the next best thing to cancer that talks: a simple blood test – a “liquid biopsy” for advanced prostate cancer. This highly sophisticated test finds traces of DNA left behind in the blood by cancer cells. Imagine following a trail of tiny, widely spaced crumbs: that’s the challenge here; there may not be that many in a sample of blood, so these remnants of cancer are not easy to find and difficult to extract.

But expertise and persistence are paying off, and once deciphered, these clues have quite a lot to say. In recent work submitted for publication, Hurley and colleagues set out to understand how mutations in the androgen receptor and other genes can predict how well advanced prostate cancer will respond to different forms of treatment. In the study, the team studied the blood of 62 Hopkins patients with metastatic castration-resistant prostate cancer (CRPC) at various points in their treatment and as cancer progressed between 2014 and 2018. “We used a ‘liquid biopsy’ to detect tumor-specific mutations in these patients before they started enzalutamide, abiraterone, or a combination of both,” says Hurley. “We found that men with a high tumor burden detected in the blood were less likely to respond to enzalutamide and abiraterone.”

In addition, they found that men with certain mutations in the androgen receptor had a shorter response to therapy, and that the loss of key genetic pathways (TP53 or PTEN) was associated with more lethal cancer.

How could these findings help patients, and what comes next? Knowing what to look for and finding these danger signs as early as possible might provide a critical window – and help doctors get the jump on the most aggressive cancer sooner, with more aggressive or gene-specific treatment.