title: Targeting the 5'-AMP-activated protein kinase and related metabolic pathways for the treatment of prostate cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Veterans Affairs Medical Center and South Florida Veterans Affairs Foundation for Research and Education , Research (151) 2A127, 1201 NW 16th St, Miami, FL 33125 , USA +1 305 5753477 ; +1 305 5753126 ; ferencrick@gmail.com.
authors.forename: Petra
authors.initials: P
authors.lastname: Popovics
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Frigo
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Schally
authors.forename: Ferenc G
authors.initials: FG
authors.lastname: Rick
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000728:Androgens; D000970:Antineoplastic Agents; C517698:CAMKK2 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D055372:AMP-Activated Protein Kinases
keywords: 5′-AMP-activated protein kinase; calcium/calmodulin-dependent protein kinase kinase 2; cancer metabolism; prostate cancer