AR-V7 protein in circulating tumor cells—the decider for therapy?
A partir d'échantillons sanguins prélevés sur 191 patients atteints d'un cancer métastatique de la prostate résistant à la castration, cette étude évalue, en fonction du traitement reçu (inhibiteur de la signalisation des récepteurs androgéniques ou taxane), l'association entre l'expression avant traitement de la protéine AR-V7 dans les cellules tumorales circulantes et la survie des patients ou, notamment, l'évolution du niveau du PSA
In this issue of JAMA Oncology, Scher et al1 present additional evidence that the presence of the constitutively active androgen receptor variant 7 (AR-V7) is a marker for resistance to standard androgen deprivation or second line androgen receptor (AR) targeting agents in men with metastatic prostate cancer. Blood samples were drawn prior to therapy and nucleated cells analyzed for protein expression by immunofluorescence for AR-V7 protein. Results were not used for clinical decision making. Remarkably, no patients with circulating tumor cells (CTCs) positive for AR-V7 protein responded to AR-directed therapy (as defined by a >50% prostate-specific antigen decline), and they had significantly worse progression-free survival and overall survival (OS) compared with patients with AR-V7–negative CTCs. These findings are in agreement with those previously reported by Antonorakis et al2 using a different messenger RNA (mRNA)-based CTC assay.2 These 2 studies provide compelling evidence that AR-V7–positive CTCs are a predictive biomarker for failure to respond to AR-directed therapy (AR-DT).
JAMA Oncology , commentaire, 2015