Journal
BIOMOLECULES
Volume 12, Issue 11, Pages -Publisher
MDPI
DOI: 10.3390/biom12111590
Keywords
androgen receptor; cancer metabolism; prostate cancer; Warburg's effect; lactate; fatty acids; drug resistance
Categories
Funding
- U.S. Department of Defense Prostate Cancer Research Program [W81XWH-17-1-0323, W81XWH-20-1-0146, W81XWH-17-1-0484]
- VA merit review award [101BX003324]
- NCI [R21CA255830, P50 CA097186]
- Institute for Prostate Cancer Research at the University ofWashington
- Fred Hutchinson Cancer Research Center
- Canadian Institutes of Health Research (CIHR) [PJT-180554]
- Mitacs Accelerate Program [IT14958]
- Prostate Cancer Foundation-British Columbia (PCFBC) Grant-in-Aid [GR025019]
- Weill Cornell Medicine SPORE in Prostate Cancer [P50CA211024]
- U.S. Department of Defense [W81XWH-191-0566]
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This article discusses the urgent need to explore new actionable targets other than the androgen receptor to improve treatment outcomes for castration-resistant prostate cancer. Tumor metabolism is considered a hallmark of cancer and understanding its relationship with androgen receptor signaling, genetic drivers, and the tumor microenvironment is important for identifying metabolic vulnerabilities. The article also provides an overview of current metabolism-based pharmacological strategies for treating castration-resistant prostate cancer.
There is an urgent need for exploring new actionable targets other than androgen receptor to improve outcome from lethal castration-resistant prostate cancer. Tumor metabolism has reemerged as a hallmark of cancer that drives and supports oncogenesis. In this regard, it is important to understand the relationship between distinctive metabolic features, androgen receptor signaling, genetic drivers in prostate cancer, and the tumor microenvironment (symbiotic and competitive metabolic interactions) to identify metabolic vulnerabilities. We explore the links between metabolism and gene regulation, and thus the unique metabolic signatures that define the malignant phenotypes at given stages of prostate tumor progression. We also provide an overview of current metabolism-based pharmacological strategies to be developed or repurposed for metabolism-based therapeutics for castration-resistant prostate cancer.
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