Researchers from Johns Hopkins University’s Kimmel Cancer Center and James Buchanan Brady Urological Institute have recently released data showing that men with advanced prostate cancer (PC) and detectable levels of androgen receptor splice variant-7 (AR-V7) respond to chemotherapy equally as men who lack AR-V7. The study, entitled, “Androgen Receptor Splice Variant 7 and Efficacy of Taxane Chemotherapy in Patients with Metastatic Castration-Resistant Prostate Cancer,” was published in the latest edition of JAMA Oncology.
Metastatic Castration-Resistant Prostate Cancer
Metastatic castration-resistant prostate cancer (MCRPC) occurs when the cancer has spread to other parts of the body, and this growth and spread has continued even after drugs or other treatments to lower the amount of male sex hormones are being administered to manage the disease.
Male sex hormones, known as androgens, are often the driving force behind prostate cancer growth, as such, a common treatment option for PC is to lower androgen levels in a man’s body. This can be accomplished by surgically removing the testicles or with drugs that stop the testicles from making androgens. This type of treatment is called hormone therapy or androgen-deprivation therapy.
In this small clinical trial of 37 MCRPC patients, researchers compared the levels of AR-V7 in patient’s blood who had received either docetaxel or cabazitaxel, two chemotherapy drugs. The results showed that of the 17 patients who had detectable levels of AR-V7, there was no statistical differences in how much their PSA levels (markers for prostate cancer) declined, how long it took for their cancers to progress or their overall survival. Another important finding was that 7 of the 17 men in the trial who carried the AR-V7 variant and received chemotherapy experienced a 50 percent reduction in their PSA levels.
In a University press release, Dr. Emmanuel Antonarakis, MD., an oncologist at the Kimmel Cancer Center and lead study author, stated “Our study shows that men who have the AR-V7 gene variant and usually don’t respond to either abiraterone or enzalutamide (hormone therapy), are not at a disadvantage when given chemotherapy drugs. It would be very useful to know if such patients are AR-V7-positive, because if they were, a better step for them might be chemotherapy rather than the alternative androgen receptor-directed hormonal therapy.”
Dr. Antonarakis’s colleague Dr. Jun Luo, PhD., the James Buchanan Brady Urological Institute researcher who discovered AR-V7, and senior study author, added, “We think AR-V7 would have the greatest utility as a biomarker to guide further treatment in men with castration-resistant prostate cancer, and not for earlier stages of the disease so far. But that’s something we should test in further studies.”
Dr. Luo, continued, “The ultimate goal is to address needs of patients who are failing standard therapy. By using the biomarker to improve patient-doctor decision-making, we could realize a therapeutic benefit without having to find a new drug.”
There is currently no commercially available test for AR-V7, but Dr.s Luo and Antonarakis, are developing an AR-V7 test that they hope to make widely available to detect AR-V7 in tumor cells circulating in patients’ blood.