Study Yields Path to Smart Treatment in Prostate Cancer

A blood test that can detect mutations in the androgen receptor can predict response to abiraterone in prostate cancer.

A molecular test that can guide providers with treatment choices is a poster child for precision medicine. Researchers from the Institute of Cancer Research in London, through a global collaboration that included scientists at the Weill Cornell College of Medicine in New York, have discovered a gene signature that can identify abiraterone-resistant prostate tumors. The results, published in Science Translational Medicine, predict non-responders to abiraterone and can prove extremely valuable if the discovery holds true in the broader population.

When the researchers sequenced 274 blood samples from 97 prostate cancer patients, they found that mutations in the androgen receptor (AR) gene could predict resistance to the drug abiraterone. This patient population harboring the mutation had poor overall survival.

Abiraterone is standard of care for men with advanced prostate cancer, but 30% to 60% of patients do not respond to the drug. The current research showed that men harboring a mutation in the AR gene or who had an amplification of AR gene, were less likely to see a decrease of more than 90% in their prostate-specific antigen levels. An interesting study finding was that the development of abiraterone resistance was associated with the appearance of either mutation in 15% of the study population, indicative of acquired resistance to the drug. The appearance of the mutated form of the receptor in the patient’s blood is valuable in cancer patients in whom repeat biopsies are not always a feasible option.

“The discovery of abiraterone was an important step forward for patients with advanced prostate cancer, but we know it doesn’t work for all men, and we’ve been searching for a marker that will tell us in advance which men will benefit. We’re delighted to have developed a test that appears to predict very accurately whether a patient will respond to abiraterone, and that it can be performed on blood samples—removing the need to take a biopsy,” said Gerhardt Attard, MD, PhD, one of the senior investigators on the paper.

The authors are now designing a prospective clinical trial to show that men with either mutation in their AR gene would fare better with chemotherapy rather than abiraterone or other drugs in the same class.