@article{86e406b2c46942ebbc29869eac60755c,
title = "Androgen receptor upregulation mediates radioresistance after ionizing radiation",
abstract = "Clinical trials have established the benefit of androgen deprivation therapy (ADT) combined with radiotherapy in prostate cancer. ADT sensitizes prostate cancer to radiotherapy-induced death at least in part through inhibition of DNA repair machinery, but for unknown reasons, adjuvant ADT provides further survival benefits. Here, we show that androgen receptor (AR) expression and activity are durably upregulated following radiotherapy in multiple human prostate cancer models in vitro and in vivo. Moreover, the degree of AR upregulation correlates with survival in vitro and time to tumor progression in animal models. We also provide evidence of AR pathway upregulation, measured by a rise in serum levels of AR-regulated hK2 protein, in nearly 20% of patients after radiotherapy. Furthermore, these men were three-fold more likely to experience subsequent biochemical failure. Collectively, these data demonstrate that radiotherapy can upregulate AR signaling after therapy to an extent that negatively affects disease progression and/or survival.",
author = "Spratt, {Daniel E.} and Evans, {Michael J.} and Davis, {Brian J.} and Doran, {Michael G.} and Lee, {Man Xia} and Neel Shah and John Wongvipat and Carnazza, {Kathryn E.} and Klee, {George G.} and William Polkinghorn and Tindall, {Donald J.} and Lewis, {Jason S.} and Sawyers, {Charles L.}",
note = "Funding Information: The authors thank the Radiochemistry & Molecular Imaging Probe Core of MSKCC (P30 CA008748) for supply of the 18F-FDHT and the MSKCC ICMIC. They also thank both the MSKCC Prostate SPORE NIH P50CA09262, the Mayo Prostate SPORE NIH P50CA091956, and the Howard Hughes Medical Institute. D.E. Spratt and M.J. Evans are funded by Rebecca and Nathan Milikowsky and David H. Koch Young Investigator Awards from the Prostate Cancer Foundation, respectively, and the authors thank them for their support. This study was supported by The Molecular Pharmacology & Chemistry Program Core (J.S. Lewis), The Radiological Society of North America 2013 Research Resident Grant #RR1350 (D.E. Spratt), the 2014 Rebecca and Nathan Milikowsky Prostate Cancer Foundation Young Investigator Award (D.E. Spratt), David H. Koch Young Investigator Award from the Prostate Cancer Foundation (M.J. Evans), the 2012 IMRAS MSKCC institutional grant (D.E. Spratt and M.J. Evans), NIH P50CA091956MAYOCLINIC SPORE (D.J. Tindall, G.G. Klee, and B.J. Davis), grant from the T.J. Martell Foundation (D.J. Tindall), NIH P50CA09262 MSKCC SPORE and the NIH P30 CA008748 (C.L. Sawyers), and the Howard Hughes Medical Institute (C.L. Sawyers). Publisher Copyright: {\textcopyright}2015 AACR.",
year = "2015",
month = nov,
day = "15",
doi = "10.1158/0008-5472.CAN-15-0892",
language = "English (US)",
volume = "75",
pages = "4688--4696",
journal = "Cancer Research",
issn = "0008-5472",
number = "22",
}