Antonarakis E.S., Lu C., Wang H., Luber B., Nakazawa M., Roeser J.C., Chen Y., Mohammad T.A., Chen Y., Fedor H.L., Lotan T.L., Zheng Q., De Marzo A.M., Isaacs J.T., Isaacs W.B., Nadal R., Paller C.J., Denmeade S.R., Carducci M.A., Eisenberger M.A., Luo J.
The New England journal of medicine 2014 371:11 (1028-1038)
The androgen-receptor isoform encoded by splice variant 7 lacks the ligand-binding domain, which is the target of enzalutamide and abiraterone, but remains constitutively active as a transcription factor. We hypothesized that detection of androgen-receptor splice variant 7 messenger RNA (AR-V7) in circulating tumor cells from men with advanced prostate cancer would be associated with resistance to enzalutamide and abiraterone. We used a quantitative reverse-transcriptase-polymerase-chain-reaction assay to evaluate AR-V7 in circulating tumor cells from prospectively enrolled patients with metastatic castration-resistant prostate cancer who were initiating treatment with either enzalutamide or abiraterone. We examined associations between AR-V7 status (positive vs. negative) and prostate-specific antigen (PSA) response rates (the primary end point), freedom from PSA progression (PSA progression-free survival), clinical or radiographic progression-free survival, and overall survival. A total of 31 enzalutamide-treated patients and 31 abiraterone-treated patients were enrolled, of whom 39% and 19%, respectively, had detectable AR-V7 in circulating tumor cells…(ver más)