Metabolomic profiling for the identification of novel diagnostic markers and therapeutic targets in prostate cancer: an update

ABSTRACT

Introduction: An altered metabolic regulation is involved in the development and progression of different cancer types. As well as this, many genes associated with tumors are shown to have an important role in control of the metabolism. The incidence of prostate cancer (PCa) is increased in men with metabolic disorders. In particular, obesity is an established risk factor for PCa. An increased body mass index correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. Increased lipogenesis is also one of the most significant events in PCa metabolism reprogramming.

Areas covered: In this article, we provide an updated review of the current understanding of the PCa metabolome and evaluate the possibility of unveiling novel therapeutic targets.

Expert opinion: Obesity is an established risk factor for PCa, and an increased BMI correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. PCa metabolome is characterized by the accumulation of metabolic intermediates and an increased expression of genes in the tricarboxylic acid cycle, the induction of de novo lipogenesis and cholesterogenesis. PCa cells can induce different alterations in their microenvironment by modulating the crosstalk between cancer and stromal cells.

KEYWORDS:

• Metabolomics
• prostate cancer
• lipid metabolism
• fatty acids
• cholesterol
• SREBP

Article Highlights

• Prostate cancer (PCa) is the most common male tumor and the second leading cause of cancer death in men worldwide. Recent estimates have calculated that in 2019, 174,650 new cases will be diagnosed and 31,620 patients will die of PCa in the United States.

• Obesity is an established risk factor for PCa, and an increased body mass index (BMI) correlates with aggressive disease, and a higher risk of biochemical recurrence and prostate cancer-specific mortality. In addition, increased BMI values are associated with disease upstaging and upgrading in low-risk PCa patients who are candidates for active surveillance.

• PCa is characterized by two distinctive metabolic fingerprints, reflecting their molecular phenotype: phospho-AKT^high/MYC^low versus phospho-AKT^low/MYC^high tumors.

• PCa metabolome is characterized by the accumulation of metabolic intermediates and an increased expression of genes in the tricarboxylic acid cycle. These findings are in accordance with the reactivation of mitochondrial aconitase, the restoration of metabolic flux through the Krebs cycle, and the induction of de novo lipogenesis and cholesterogenesis.

• PCa cells are able to induce different alterations in their microenvironment by modulating the crosstalk between cancer and stromal cells.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.