Abstract
Background: The development of effective screening methods for early cancer detection is one of the foremost challenges facing modern cancer research. Urinary metabolomics has recently emerged as a potentially transformative approach to cancer biomarker discovery owing to its noninvasive sampling characteristics and robust analytical feasibility. Objective: To provide an overview of new developments in urinary metabolomics, cover the most promising aspects of hyphenated techniques in untargeted and targeted metabolomics, and to discuss technical and clinical limitations in addition to the emerging challenges in the field of urinary metabolomics and its application to cancer biomarker discovery. Methods: A systematic review of research conducted in the past five years on the application of urinary metabolomics to cancer biomarker discovery was performed. Given the breadth of this topic, our review focused on the five most widely studied cancers employing urinary metabolomics approaches, including lung, breast, bladder, prostate, and ovarian cancers. Results: As an extension of conventional metabolomics, urinary metabolomics has benefitted from recent technological developments in nuclear magnetic resonance, mass spectrometry, gas and liquid chromatography, and capillary electrophoresis that have improved urine metabolome coverage and analytical reproducibility. Extensive metabolic profiling in urine has revealed a significant number of altered metabolic pathways and putative biomarkers, including pteridines, modified nucleosides, and acylcarnitines, that have been associated with cancer development and progression. Conclusion: Urinary metabolomics presents a transformative new approach toward cancer biomarker discovery with high translational capacity to early cancer screening.