Androgen receptor burden and poor response to abiraterone or enzalutamide in TP53 wild-type metastatic castration-resistant prostate cancer

JAMA Jul 18, 2019

De Laere B, et al. - Experts hypothesized that long-term chemical castration, alongside the cancer treatment trajectory, would ultimately lead to perturbed androgen receptor (AR) biomarker output in all subjects. Multiple biomarker evaluations of AR were required in order to recognize AR signaling inhibitors (ARSis)-sensitive subjects, in this scenario. Via comprehensive liquid biopsy AR profiling, how AR perturbations suffered prognostic value when correcting for tumor burden estimates and clinical variables had been exhibited previously. In subjects with metastatic castration-resistant prostate cancer, AR molecular perturbations in liquid biopsy specimens (circulating tumor cells and circulating tumor DNA) was correlated with poorer results on the ARSis abiraterone or enzalutamide, with opposite claims concerning the clinical use of AR splice variant 7 or AR amplification status. Hence, it was concluded that AR-driven biomarkers were exceeded by TP53 alterations, recording that 71.3% and 97.9% of subjects had related AR-driven biomarkers at baseline and progression, respectively, consistent with others’ conclusions.
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