title: Insulin-like growth factor pathway: a link between androgen deprivation therapy (ADT), insulin resistance, and disease progression in patients with prostate cancer?
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. rahul.aggarwal@ucsf.edu
authors.forename: Rahul R
authors.initials: RR
authors.lastname: Aggarwal
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Ryan
authors.forename: June M
authors.initials: JM
authors.lastname: Chan
mesh_terms: D000726:Androgen Antagonists / Q000627:therapeutic use*; D018450:Disease Progression; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D015398:Signal Transduction
chemical_list: D000726:Androgen Antagonists; D007334:Insulin-Like Growth Factor I