Has the time arrived for biomarker-directed therapy in castration-resistant prostate cancer?
Menée sur 37 patients atteints d'un cancer métastatique de la prostate résistant à la castration et traités par une chimiothérapie à base de taxane (docétaxel ou cabazitaxel), cette étude évalue l'association entre la détection d'un variant d'épissage du récepteur des androgènes (AR-V7) dans des cellules tumorales circulantes et l'apparition d'une résistance thérapeutique
Men with advanced prostate cancer live for years while receiving sequential cancer treatments that are costly and associated with morbidity. The mainstay of systemic treatment is androgen deprivation therapy aimed at abrogating critical androgen receptor (AR) directed growth, but it invariably leads to the development of castration-resistant prostate cancer (CRPC). There are 7 approved therapies for metastatic CRPC (mCRPC) but no prospective validated data to guide individualized treatment or the sequence of treatments. Many men with CRPC respond to secondary hormonal treatments such as CYP17A1 inhibitors (abiraterone) or to a more potent AR antagonist (enzalutamide), but responses are not durable. One mechanism that contributes to resistance is alternative splicing of the AR to generate AR variants (AR-Vs) that lack the ligand-binding domain and therefore no longer require androgen; AR variant 7 (AR-V7) is the most commonly expressed AR-V/ Studies evaluating AR-V7 reported by Antonarakis et al first in the context of abiraterone and enzalutamide therapy and in this issue of JAMA Oncology with taxane therapy provide promise for AR-V7 as the first predictive biomarker in CRPC.
JAMA Oncology , éditorial en libre accès, 2014