2014 September 11; 371(11): 1028–1038. | Emmanuel S. Antonarakis, M.D., Changxue Lu, Ph.D., Hao Wang, Ph.D., Brandon Luber, Sc.M., Mary Nakazawa, M.H.S., Jeffrey C. Roeser, B.S., Yan Chen, Ph.D., Tabrez A. Mohammad, Ph.D., Yidong Chen, Ph.D., Helen L. Fedor, B.S., Tamara L. Lotan, M.D., Qizhi Zheng, M.D., Angelo M. De Marzo, M.D., Ph.D., John T. Isaacs, Ph.D., William B. Isaacs, Ph.D., Rosa Nadal, M.D., Channing J. Paller, M.D., Samuel R. Denmeade, M.D., Michael A. Carducci, M.D., Mario A. Eisenberger, M.D., and Jun Luo, Ph.D
This study investigates the association between the presence of androgen-receptor splice variant 7 (AR-V7) in circulating tumor cells and resistance to enzalutamide and abiraterone in patients with castration-resistant prostate cancer. AR-V7, which lacks the ligand-binding domain of the androgen receptor, remains constitutively active as a transcription factor. The study enrolled 62 patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. AR-V7 was detected in circulating tumor cells in 39% of enzalutamide-treated patients and 19% of abiraterone-treated patients. Patients with detectable AR-V7 had lower rates of prostate-specific antigen (PSA) response, shorter PSA progression-free survival, clinical or radiographic progression-free survival, and overall survival compared to those without detectable AR-V7. The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for the expression of full-length androgen receptor mRNA. These findings suggest that AR-V7 detection in circulating tumor cells may be a biomarker for resistance to enzalutamide and abiraterone, but further large-scale prospective validation is needed.This study investigates the association between the presence of androgen-receptor splice variant 7 (AR-V7) in circulating tumor cells and resistance to enzalutamide and abiraterone in patients with castration-resistant prostate cancer. AR-V7, which lacks the ligand-binding domain of the androgen receptor, remains constitutively active as a transcription factor. The study enrolled 62 patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. AR-V7 was detected in circulating tumor cells in 39% of enzalutamide-treated patients and 19% of abiraterone-treated patients. Patients with detectable AR-V7 had lower rates of prostate-specific antigen (PSA) response, shorter PSA progression-free survival, clinical or radiographic progression-free survival, and overall survival compared to those without detectable AR-V7. The association between AR-V7 detection and therapeutic resistance was maintained after adjustment for the expression of full-length androgen receptor mRNA. These findings suggest that AR-V7 detection in circulating tumor cells may be a biomarker for resistance to enzalutamide and abiraterone, but further large-scale prospective validation is needed.