Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to 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.

Automated summary

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.