Research on presence of AR-V7 in prostate cancer patients

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Detecting AR-V7 positive tumor cells circulating in the blood of an advanced prostate cancer patient predicts that he will not only fail the commonly-prescribed androgen receptor signaling inhibitors (ARSI), abiraterone and enzalutamide, but that he will survive significantly longer if treated with a taxane based chemotherapy regimen.

This discovery, published today in  JAMA Oncology, emerged from a study of 161 progressing metastatic castration-resistant prostate cancer (mCRPC) patients about to start an FDA approved ARSIs or taxane as a first, second or third line treatment at Memorial Sloan Kettering Cancer Center (MSK). Blood samples taken along with those routinely collected from the patients were analyzed on the Epic Sciences’ liquid biopsy platform for circulating tumor cells (CTCs) with the AR-V7 biomarker. Overall, almost 20% of patients had AR-V7 positive CTCs.

“The percentage of men that responds to ARSIs is highest in the first line setting, decreasing steadily as more treatments are given. We found that a novel liquid biopsy for AR-V7 was able to identify, with specificity, patients who will not benefit from these therapies and should instead start chemotherapy independent of the line of therapy being administered,” said Howard Scher, M.D., chief of the genitourinary oncology services at MSK and corresponding author for the study.

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Virtually all men with metastatic prostate cancer eventually develop mCRPC, an advanced state of the disease where the standard of care includes abiraterone, enzalutamide and taxanes. Although these therapies extend the lives of many men, approximately 20–25% of patients fail to respond in the first line, which increases to 60–70% in the second line setting. Worse is that determining non-response is often delayed, which may compromise the chance to benefit from alternative treatments.

A possible means for identifying non-responders emerged in 2014, when Johns Hopkins researchers discovered many patients’ CTCs had the AR-V7 splice variant.

“We wanted to determine AR-V7’s potential for guiding treatment decisions by assessing a real world sample from any mCRPC patient coming to Memorial Sloan Kettering Cancer Center,” said Ryan Dittamore, co-investigator on the JAMA Oncology study and vice president of translational research and clinical affairs at Epic Sciences.

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The researchers found that every AR-V7 positive patient identified by the Epic Sciences test failed to respond to abiraterone and enzalutamide, and experienced faster disease progression and shorter overall survival than AR-V7 negative patients.  Additionally, patients who were AR-V7 positive survived longer when treated with taxane chemotherapies rather than abiraterone or enzalutamide (median 8.9 vs. 4.6 months). In multivariate models taking into account line of therapy and other critical clinical measures, patients who were AR-V7 positive had a 75.8% reduction of risk of death on taxane chemotherapy than on abiraterone or enzalutamide.

“This study indicates the potential for an AR-V7 predictive test to enable advanced prostate cancer patients to avoid ineffective therapies and to receive chemotherapy at an earlier stage when it may be more beneficial. Today no predictive diagnostic tests are available to improve treatment selection in prostate cancer—and they are urgently needed,” said Murali Prahalad, Ph.D., CEO of Epic Sciences.

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The Epic Sciences liquid biopsy platform used in the study images every nucleated cell in patients’ blood to find those with the AR-V7 protein in the nucleus of all potential categories of CTCs, including non-traditional CTCs that are clustered or lack traditional protein markers such as cytokeratin (CK) or EpCAM. This allows identification, on a single cell basis, of rare subpopulations of metastatic cancer cells that may be resistant or susceptible to specific cancer therapies. – PRNewswire

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