Journal
CANCER DISCOVERY
Volume 2, Issue 11, Pages 995-1003Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2159-8290.CD-12-0222
Keywords
-
Categories
Funding
- Evans Foundation
- Prostate Cancer Foundation (PCF)
- Program of the Entertainment Industry Foundation [SU2C-AACR-DT0309]
- T.J. Martell Foundation
- Starr Cancer Consortium
- Susan G. Komen for the Cure [KG090412]
- NCI-MGH Federal Share Program
- Department of Defense Physician Research Training Awards
- Mazzone-DF/HCC Career Development Award
- Conquer Cancer Foundation Career Development Award
- PCF Young Investigator Award
- American Cancer Society
- Howard Hughes Medical Institute
- Stand Up To Cancer Dream Team Translational Cancer Research Grant
- [NIH-NIBIB-5R01EB008047]
- [NCI-CA129933]
- [NCI-C06-CA-059267]
- [NIH-5K12CA87723-09]
Ask authors/readers for more resources
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. SIGNIFICANCE: Acquired resistance to first-line hormonal therapy in prostate cancer is heterogeneous in the extent of AR pathway reactivation. Measurement of pre- and posttreatment AR signaling within CTCs may help target such treatments to patients most likely to respond to second-line therapies. Cancer Discov; 2(11); 995-1003. (C) 2012 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available