The dark side of lipid metabolism in prostate and renal carcinoma: novel insights into molecular diagnostic and biomarker discovery

ABSTRACT

Introduction

Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer’s aberrant pathways has also been demonstrated.

Areas covered

This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient’s risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies.

Expert opinion

Lipidomics is a promising branch of ‘omics’ approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.

KEYWORDS:

• Biomarker
• lipidomics
• metabolomics
• metabolism
• prostate cancer
• renal cell carcinoma

Article highlights

• Fatty acids (FAs) levels in RCC and PCa cells may be caused by elevated absorption or by increased de novo lipogenesis. Malignancies such as RCC that have a higher risk of disease recurrence and mortality, frequently have fatty acid synthase (FASN) overexpression. Numerous studies have shown that blocking lipogenic enzymes like FASN inhibits the development of malignant cells and induces apoptosis in PCa and RCC.

• Elongases, may prevent lipotoxicity-driven apoptosis by promoting tumor growth and progression in RCC via preserving endoplasmic reticulum homeostasis. Depletion of ELOVL5 increased the production of reactive oxygen species and suppressed the proliferation of PCa cells

• Dysregulated cholesterol also plays a role in the development of PCa and RCC. Numerous studies on 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase and statins demonstrated their potential use in urological malignancies. Using statins is linked to longer cancer-specific and overall survival (OS) in PCa patients and their use with mTOR inhibitors could work together to limit the proliferation of RCC.

• Lipidomics finds its potential application in biomarker detection, drug efficacy monitoring and response evaluation. A lipidomic panel could become a prospective diagnostic biomarker for separating benign prostatic tissues from PCa in humans with good sensitivity, specificity, and accuracy. Blood lipid content help to distinguish between responders and non-responders during the first and third cycles of immunotherapy for RCC with a good potential predictive value.

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.