Recently, a study led by researchers at the Johns Hopkins University Sidney Kimmel Comprehensive Cancer Research Center showed that if the tumors of prostate cancer patients contain a protein called AR-V7, which can be detected in the blood, they After treatment with two widely used drugs for metastatic prostate cancer, there is likely to be no effect.
Researchers said that if these results can be verified through large-scale studies, then if a prostate cancer patient has detectable blood levels of ARV7, he should avoid these two drugs and take other medications instead.
The study evaluated two groups (31) of prostate cancer patients who had spread. Although they had low levels of testosterone, their blood prostate-specific antigen (PSA) levels still rose. Researchers gave each patient enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, thereby indicating whether the drug worked. In the enzalutamide group, 12 patients who tested positive for AR-V7 in their blood did not respond to the drug, while 10 of the 19 patients who did not detect AR-V7 responded to the drug. In the abiraterone group, all 6 AR-V7-positive patients did not respond to the drug, while 17 of the 25 AR-V7-deficient patients responded to the drug.
Dr. Emmanuel Antonarakis, assistant professor of oncology at Johns Hopkins University, said that enzalutamide and abiraterone can prolong the life of about 80% of prostate cancer patients very successfully, but these two drugs are used in the remaining 20% of prostate patients. Does not work.
Antonarakis said: "Until now, we have not been able to predict which patients will not respond to these therapies. If our results are verified by other researchers, then blood tests can use AR-V7 as a biomarker to predict endangerment. The resistance of luminamide and abiraterone allows us to guide patients who test positive for AR-V7 to receive other types of treatment as soon as possible, saving time and money, while avoiding ineffective treatments."
Prostate cancer relies on male sex hormones (including testosterone) to grow. Enzalutamide and abiraterone target proteins called androgen receptors, blocking the receptor's ability to activate prostate cancer cells. AR-V7 is a shortened androgen receptor that lacks the binding sites targeted by enzalutamide and abiraterone. Without the binding sites of these two drugs, AR-V7 can manipulate the genetic material of prostate cancer cells arbitrarily, which makes the cancer cells grow and spread.
Antonarakis and his colleague Dr. Jun Luo-he discovered AR-V7 for the first time in 2008 and also tracked the patient's progression-free survival (referring to the time span from the beginning of treatment of the tumor to the appearance of secondary growth of the tumor) and Overall survival rate. They found that among patients treated with enzalutamide, the progression-free survival of AR-V7-positive patients was 2.1 months, while that of AR-V7-negative patients was 6.1 months, and the overall survival rate was between AR-V7-positive and AR-V7-positive patients. The negative patients were 5.5 months and 9 months respectively. Similarly, among patients treated with abiraterone, the progression-free survival of AR-V7 positive and negative patients was 2.3 months and 6 months, respectively, and the overall survival rate was 10.6 months and 12 months, respectively. The researchers warned that most of the patients in the study had advanced tumors and had previously received multiple treatments, so their prognostic results may not be able to summarize all prostate patients.
Antonarakis said: “Patients with AR-V7 in their blood samples did not benefit from the two treatments of enzalutamide and abiraterone.” He added that shortened AR-V7 protein may have been present at the beginning of treatment. Obtained in a patient’s blood sample or after treatment has already started. He said: "This test can be used before the start of enzalutamide and abiraterone therapy. If the test results show the presence of AR-V7, the patient can choose other different treatments. It can also be used to monitor receiving enzalutamide. The blood of patients treated with abiraterone is AR-V7, thus indicating whether these drugs will work for a long time."