499 656
Platinum Priority – Prostate Cancer
Editorial by Joy C. Yang and Christopher P. Evans on pp. 507–508 of this issue
Co-clinical Analysis of a Genetically Engineered Mouse Model and
Human Prostate Cancer Reveals Significance of
NKX3.1
Expression
for Response to 5
a
-reductase Inhibition
Aditya Dutta
a ,Sukanya Panja
b ,Renu K. Virk
c ,Jaime Yeji Kim
d ,Roseann Zott
e ,Serge Cremers
f ,David M. Golombos
g ,Deli Liu
h ,Juan Miguel Mosquera
i ,Elahe A. Mostaghel
j ,Christopher E. Barbieri
k ,Antonina Mitrofanova
b[10_TD$DIFF]
, * ,Cory Abate-Shen
l[11_TD$DIFF]
, *a
Departments of Medicine and Urology, Institute of Cancer Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New
York, NY, USA;
b
Department of Health Informatics, Rutgers School of Health Professions, Rutgers Biomedical and Health Sciences, Newark, NJ, USA;
c
Department of Pathology and Cell Biology, Columbia University Medical Center, NY, USA;
d
Department of Medicine, Herbert Irving Comprehensive Cancer
Center, Columbia University Medical Center, New York, NY, USA;
e
The Irving Institute for Clinical and Translational Medicine, Columbia University Medical
Center, New York, NY, USA;
f
Departments of Pathology & Cell Biology and Medicine, The Irving Institute for Clinical and Translational Medicine, Columbia
University Medical Center, New York, NY, USA;
g
Department of Urology, Weill Cornell Medicine, New York, NY, USA;
h
Department of Urology, HRH Prince
Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, New York,
[3_TD$DIFF]
USA;
i
Department of
Pathology and Laboratory Medicine, Englander Institute for Precision Medicine, Weill Cornell Medicine and New York
[12_TD$DIFF]
-Presbyterian Hospital, New York, NY,
USA;
j
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA;
k
Department of Urology, Sandra and Edward Meyer Cancer
Center, Weill Cornell Medicine, New York, NY, USA;
l
[5_TD$DIFF]
Departments of Urology, Medicine, Pathology & Cell Biology, and Systems Biology, Institute of Cancer
Genetics, Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) 4 9 9 – 5 0 6ava ilable at
www.sciencedirect.comjournal homepage:
www.eu ropeanurology.comArticle info
Article history:
Accepted March 21, 2017
Associate Editor:
Christian Gratzke
Keywords:
5
a
-Reductase inhibitors
Active surveillance
Chemoprevention
Dutasteride
Finasteride
NKX3.1
Precision cancer prevention
Prostate cancer
Abstract
Background:
Although men on active surveillance for prostate cancer (PCa) may benefit
from intervention with 5
a
-reductase inhibitors (5-ARIs), it has not been resolved
whether 5-ARIs are effective for delaying disease progression and, if so, whether specific
patients are more likely to benefit.
Objective:
To identify molecular features predictive of patient response to 5-ARIs.
Design, setting, and participants:
Nkx3.1
mutant mice, a model of early-stage PCa, were
treated with the 5-ARI finasteride, and histopathological and molecular analyses were
performed. Cross-species computational analyses were used to compare expression
profiles for treated mice with those of patients who had received 5-ARIs before
prostatectomy.
Intervention:
Finasteride administered to
Nkx3.1
mutant mice. 5-ARI-treated patient
specimens obtained retrospectively.
Outcome measurements and statistical analysis:
Endpoints in mice included histopa-
thology, immunohistochemistry, and molecular profiling. GraphPad Prism software, R-
studio, and Matlab were used for statistical and data analyses.
Results and limitations:
Finasteride treatment of
Nkx3.1
mutant mice resulted in a
significant reduction in prostatic intraepithelial neoplasia (PIN), as evident from
* Corresponding authors. Department of Health Informatics, Rutgers School of Health Professions,
Rutgers Biomedical and Health Sciences, Stanley S. Bergen Jr. Building, 65 Bergen Street, Newark, NJ
07107, USA.
[6_TD$DIFF]
Irving Cancer Research Center, 1130 Saint Nicholas Avenue, New York, NY 10032, USA.
Tel. +1-212-851-4735; Fax: +1-212-851-4787.
E-mail addresses:
antonina.mitrofanova@rutgers.edu(A. Mitrofanova),
cabateshen@columbia.edu(C. Abate-Shen).
http://dx.doi.org/10.1016/j.eururo.2017.03.0310302-2838/
#
2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.