TY - JOUR
T1 - Targeting the 5′-AMP-activated protein kinase and related metabolic pathways for the treatment of prostate cancer
AU - Popovics, Petra
AU - Frigo, Daniel E.
AU - Schally, Andrew V.
AU - Rick, Ferenc G.
N1 - Funding Information:
The authors were supported by a stipend program of the Department of Medicine, Dresden and by the Helmholtz Alliance ICEMED (Imaging and Curing Environmental Metabolic Diseases) through the Initiative and Networking Fund of the Helmholtz Association (to Popovics P), DoD/ PCRP grant W81XWH-12-1-0204 and a grant from the Golfers Against Cancer (to Frigo DE), the Medical Research Service of the Veterans Affairs Department, Departments of Pathology and Medicine, Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, University of Miami, Miller School of Medicine, the South Florida Veterans Affairs Foundation for Research and Education (all to Schally AV); Urology Care Foundation Research Scholars Program and the American Urological Association (AUA) Southeastern Section (to Rick FG). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
Publisher Copyright:
© 2015 Informa UK, Ltd.
Copyright:
Copyright 2015 Elsevier B.V., All rights reserved.
PY - 2015/5/1
Y1 - 2015/5/1
N2 - Introduction: Increasing evidence suggests that prostate cancer cells undergo unique metabolic reprogramming during transformation. A master regulator of cellular homeostasis, 5′-AMP-activated protein kinase (AMPK), directs metabolic adaptation that supports the growth demands of rapidly dividing cancer cells. The utilization of AMPK as a therapeutic target may therefore provide an effective strategy in the treatment of prostate cancer.Areas covered: Our review describes the regulation of AMPK by androgens and upstream kinases including the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in prostate cancer. Oncogenic, AMPK-regulated pathways that direct various metabolic processes are also addressed. Furthermore, we discuss the role of AMPK in growth arrest and autophagy as a potential survival pathway for cancer cells. In addition, by regulating non-metabolic pathways, AMPK may stimulate migration and mitosis. Finally, this review summarizes efforts to treat prostate cancer with pharmacological agents capable of modulating AMPK signaling.Expert opinion: Current research is primarily focused on developing drugs that activate AMPK as a treatment for prostate cancer. However, oncogenic aspects of AMPK signaling calls for caution about employing such therapies. We think that inhibitors of CaMKK2 or AMPK, or perhaps the modulation of downstream targets of AMPK, will gain importance in the clinical management of prostate cancer.
AB - Introduction: Increasing evidence suggests that prostate cancer cells undergo unique metabolic reprogramming during transformation. A master regulator of cellular homeostasis, 5′-AMP-activated protein kinase (AMPK), directs metabolic adaptation that supports the growth demands of rapidly dividing cancer cells. The utilization of AMPK as a therapeutic target may therefore provide an effective strategy in the treatment of prostate cancer.Areas covered: Our review describes the regulation of AMPK by androgens and upstream kinases including the calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) in prostate cancer. Oncogenic, AMPK-regulated pathways that direct various metabolic processes are also addressed. Furthermore, we discuss the role of AMPK in growth arrest and autophagy as a potential survival pathway for cancer cells. In addition, by regulating non-metabolic pathways, AMPK may stimulate migration and mitosis. Finally, this review summarizes efforts to treat prostate cancer with pharmacological agents capable of modulating AMPK signaling.Expert opinion: Current research is primarily focused on developing drugs that activate AMPK as a treatment for prostate cancer. However, oncogenic aspects of AMPK signaling calls for caution about employing such therapies. We think that inhibitors of CaMKK2 or AMPK, or perhaps the modulation of downstream targets of AMPK, will gain importance in the clinical management of prostate cancer.
KW - 5′-AMP-activated protein kinase
KW - Calcium/calmodulin-dependent protein kinase kinase 2
KW - Cancer metabolism
KW - Prostate cancer
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U2 - 10.1517/14728222.2015.1005603
DO - 10.1517/14728222.2015.1005603
M3 - Review article
C2 - 25600663
AN - SCOPUS:84928502222
VL - 19
SP - 617
EP - 632
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
SN - 1472-8222
IS - 5
ER -