Mini-symposium: diagnostic molecular pathologyThe pathogenesis of prostate cancer: from molecular to metabolic alterations
Section snippets
Epidemiology
Among the male population of the USA, prostate cancer is the most prevalent non-cutaneous neoplasm (1 in 6 men will be diagnosed with PCa cancer during their lifetime) and a leading cause of cancer-related death, second only to lung and colon cancer.1 Its frequency varies widely, with the highest rates reported in Western countries, and the lowest rates in Asia.2 Multiple factors contribute to the high incidence and prevalence of PCa. Risk factors include age, family history and race, but also
Genetic mutations and epigenetic changes in prostate cancer
Analyses of polymorphic microsatellites have shown that multiple foci of cancer arise independently within the same prostate.9 An increasing number of studies prove that prostate cancer can be genetically classified into different subgroups, exemplifying the extensive phenotypic and molecular heterogeneity of this disease. Genetic profile analyses have detected only a few, potentially significant mutations in hereditary and sporadic prostate cancer.
Metabolic alterations in tumour initiation and in androgen-independent disease
Pioneering efforts on the characterization of tumour metabolism have revealed that cancer cells rely on anaerobic pathways to convert glucose to ATP, even in abundant oxygen.23 This phenomenon, known as the Warburg effect, occurs despite the fact that the anaerobic pathway is less efficient for energy supply than aerobic respiration.
Warburg claimed that the first phase of cancer genesis is irreversible injury to the respiratory chain. Due to the resulting defective aerobic energy production,
Conclusions
In this review, the authors suggested that interfering with lipid metabolism has detrimental effects on prostate tumour cell survival. Studies are under way to determine the precise mechanisms responsible for tumour initiation and maintenance by altered metabolic pathways.
From a broader perspective, the authors would like to underscore the necessity of more thorough investigations of the metabolic alterations in cancer, and speculate that combining metabolic profiling with genome-wide analyses
Acknowledgments
We thank members of Loda laboratory for fruitful discussions, particularly Emanuele Palesandolo, Carmen Priolo, Stephen Finn and Giorgia Zadra; Sonal Jhaveri-Schneider for critical review of the manuscript; Marleen Marino and Jane Hayward for graphic assistance.
This work was supported by the Gelb Center for genitourinary oncology and by grants from the NIH (Specialized Programs of Research Excellence 5P50CA90381, PO1 CA089021) and the Prostate Cancer Foundation (Massimo Loda). ML is a Novartis
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Cited by (23)
Quantitative proteomics reveals that enzymes of the ketogenic pathway are associated with prostate cancer progression
2013, Molecular and Cellular ProteomicsCitation Excerpt :One avenue through which such an effect can be achieved is to increase energy production through the breakdown of fatty acids via the β-oxidation pathway (49). Fatty acid oxidation has been widely studied with respect to prostate cancer progression, specifically, as a means of providing an important source of bioenergy (49, 50). Various proteins involved in the metabolism of fatty acids have been determined to be altered during prostate cancer (49, 50).
Prediction of capillary gas chromatographic retention times of fatty acid methyl esters in human blood using MLR, PLS and back-propagation artificial neural networks
2011, TalantaCitation Excerpt :During the past two decades, determination of fatty-acid content in bio-fluids, such as blood and plasma, has emerged into an intense focus of research in several areas, including, e.g. environmental chemistry, food science, and medicine [1,2]. The determination of different classes of fatty acids in human blood is very important because it could caused the certain human cancers, including carcinoma of the breast [3], prostate [4], colon [5], ovary [6] and endometrium [7] at the high levels of fatty acid. However, due to the diversity of fatty acids in terms of their chain length, branching, degree of unsaturation, geometry and position of the double bonds, as well as the presence of other substituents and annular structures their analysis is still a challenge today [8].
Molecular basis and therapeutic targets in prostate cancer: A comprehensive review
2023, Biomolecules and BiomedicineCRISP3 glycoprotein: A good biomarker for prostate cancer?
2021, Jornal Brasileiro de Patologia e Medicina LaboratorialGC-MS-based untargeted metabolomics of plasma and urine to evaluate metabolic changes in prostate cancer
2020, Journal of Breath Research