TY - JOUR
T1 - Insulin-like growth factor pathway
T2 - A link between androgen deprivation therapy (ADT), insulin resistance, and disease progression in patients with prostate cancer?
AU - Aggarwal, Rahul
AU - Ryan, Charles J.
AU - Chan, June M.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - Androgen deprivation therapy (ADT) is standard of care for patients with metastatic hormone-sensitive prostate cancer (HSPC), yet through its induction of a hypogonadal state leads to metabolic perturbations, including insulin resistance (IR) and obesity. IR and obesity have been associated with an increased risk of progression to castrate-resistant prostate cancer (CRPC) and ultimately increased prostate cancer-specific mortality. On a molecular level, this association between obesity/IR and prostate cancer progression may be mediated by alterations in the insulin-like growth factor (IGF) axis, which has been shown to be up-regulated upon disease progression to CRPC. Targeting the IGF axis, either by anti-IGF therapy or via enhancement of peripheral insulin sensitivity, represents a viable therapeutic target in patients with prostate cancer. Using the development of IR and/or obesity may represent a clinically available biomarker that may predict those patients most likely to respond to such therapy, and warrants testing in future prospective clinical trials.
AB - Androgen deprivation therapy (ADT) is standard of care for patients with metastatic hormone-sensitive prostate cancer (HSPC), yet through its induction of a hypogonadal state leads to metabolic perturbations, including insulin resistance (IR) and obesity. IR and obesity have been associated with an increased risk of progression to castrate-resistant prostate cancer (CRPC) and ultimately increased prostate cancer-specific mortality. On a molecular level, this association between obesity/IR and prostate cancer progression may be mediated by alterations in the insulin-like growth factor (IGF) axis, which has been shown to be up-regulated upon disease progression to CRPC. Targeting the IGF axis, either by anti-IGF therapy or via enhancement of peripheral insulin sensitivity, represents a viable therapeutic target in patients with prostate cancer. Using the development of IR and/or obesity may represent a clinically available biomarker that may predict those patients most likely to respond to such therapy, and warrants testing in future prospective clinical trials.
KW - Androgen deprivation therapy
KW - Castration-resistant
KW - Insulin resistance
KW - Insulin-like growth factor
KW - Prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=84874102233&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874102233&partnerID=8YFLogxK
U2 - 10.1016/j.urolonc.2011.05.001
DO - 10.1016/j.urolonc.2011.05.001
M3 - Review article
C2 - 21658978
AN - SCOPUS:84874102233
SN - 1078-1439
VL - 31
SP - 522
EP - 530
JO - Urologic Oncology: Seminars and Original Investigations
JF - Urologic Oncology: Seminars and Original Investigations
IS - 5
ER -