Targeting the 5′-AMP-activated protein kinase and related metabolic pathways for the treatment of prostate cancer
| Autor: | Daniel E. Frigo, Petra Popovics, Ferenc G. Rick, Andrew V. Schally |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Clinical Biochemistry Antineoplastic Agents Calcium-Calmodulin-Dependent Protein Kinase Kinase AMP-Activated Protein Kinases Prostate cancer Drug Discovery medicine Animals Humans ASK1 Molecular Targeted Therapy Protein kinase A CAMKK2 Pharmacology biology Akt/PKB signaling pathway Cyclin-dependent kinase 4 Cyclin-dependent kinase 2 Prostatic Neoplasms AMPK medicine.disease Cell biology Drug Design Androgens biology.protein Molecular Medicine Signal Transduction |
| Zdroj: | Expert Opinion on Therapeutic Targets. 19:617-632 |
| ISSN: | 1744-7631 1472-8222 |
| Popis: | 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.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.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. |
| Databáze: | OpenAIRE |
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