Androgen deprivation therapy (ADT) is initially effective in treating metastatic prostate cancer, and secondary hormonal therapies are being tested to suppress androgen receptor (AR) reactivation in castration-resistant prostate cancer (CRPC).
Despite variable responses to AR pathway inhibitors in CRPC, there are no reliable biomarkers to guide their application. Here, we used microfluidic capture of circulating tumor cells (CTC) to measure AR signaling readouts before and after therapeutic interventions. Single-cell immunofluorescence analysis revealed predominantly "AR-on" CTC signatures in untreated patients, compared with heterogeneous ("AR-on, AR-off, and AR-mixed") CTC populations in patients with CRPC. Initiation of first-line ADT induced a profound switch from "AR-on" to "AR-off" CTCs, whereas secondary hormonal therapy in CRPC resulted in variable responses. Presence of "AR-mixed" CTCs and increasing "AR-on" cells despite treatment with abiraterone acetate were associated with an adverse treatment outcome. Measuring treatment-induced signaling responses within CTCs may help guide therapy in prostate cancer.
Written by:
Miyamoto DT, Lee RJ, Stott SL, Ting DT, Wittner BS, Ulman M, Smas ME, Lord JB, Brannigan BW, Trautwein J, Bander NH, Wu CL, Sequist LV, Smith MR, Ramaswamy S, Toner M, Maheswaran S, Haber DA. Are you the author?
Massachusetts General Hospital Cancer Center, Center for Bioengineering in Medicine and Departments of Radiation Oncology, Medicine, Surgery and Pathology, Harvard Medical School, Charlestown, Massachusetts; Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York; and Howard Hughes Medical Institute, Chevy Chase, Maryland.
Reference: Cancer Discov. 2012 Nov;2(11):995-1003.
doi: 10.1158/2159-8290.CD-12-0222
PubMed Abstract
PMID: 23093251
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