[HTML][HTML] Prospective evaluation of clinical outcomes using a multiplex liquid biopsy targeting diverse resistance mechanisms in metastatic prostate cancer
JM Sperger, H Emamekhoo, RR McKay… - Journal of Clinical …, 2021 - ncbi.nlm.nih.gov
Journal of Clinical Oncology, 2021•ncbi.nlm.nih.gov
PURPOSE Nearly all men with prostate cancer treated with androgen receptor (AR)
signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including
constitutive activation of the AR pathway, driven by AR genomic structural alterations,
expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity
termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI
resistance mechanisms is critical for optimizing therapy. MATERIALS AND METHODS A …
signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including
constitutive activation of the AR pathway, driven by AR genomic structural alterations,
expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity
termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI
resistance mechanisms is critical for optimizing therapy. MATERIALS AND METHODS A …
PURPOSE
Nearly all men with prostate cancer treated with androgen receptor (AR) signaling inhibitors (ARSIs) develop resistance via diverse mechanisms including constitutive activation of the AR pathway, driven by AR genomic structural alterations, expression of AR splice variants (AR-Vs), or loss of AR dependence and lineage plasticity termed neuroendocrine prostate cancer. Understanding these de novo acquired ARSI resistance mechanisms is critical for optimizing therapy.
MATERIALS AND METHODS
A novel liquid biopsy technology was used to collect mRNA from circulating tumor cells (CTCs) to measure expression of AR-Vs, AR targets, and neuroendocrine prostate cancer markers. An institutional review board–approved prospective cohort (N= 99) was used to identify patterns of gene expression. Two prospective multicenter phase II clinical trials of ARSIs for men with castration-resistant prostate cancer (ClinicalTrials. gov:
ncbi.nlm.nih.gov
