CMPtIMSMS · Cancer metabolic profiling through ion mobility and mass spectrometric-based methods

Cancer is a leading cause of death and there is little doubt regarding the importance of its early detection, in order to reduce both mortality and healthcare costs. In this regard, metabolomics is becoming a popular approach on the prowl for early diagnosis of cancer.Because biomarker discovery requires the analysis of numerous samples of high complexity, the development of high-throughput analytical platforms is of great interest. One such technology is ion mobility-mass spectrometry (IMS-MS). However, interfacing traditional drift-tube IMS with commercial MS requires substantial modifications of the latter, precluding its rapid expansion in metabolomic studies. Alternatively, differential mobility analyzers (DMA) are more easily combinable with commercial MS. We propose here to use a DMA-MS system to interrogate the metabolic phenotype of lung cancer tissue extracts.Complementarily to this plan, we intend to execute a second research strategy. Exhaled breath provides a continuous window to the biochemical activity within a person, and so holds promise as a diagnostic tool. However, in spite of the important milestones achieved following different approaches during the recent years, several issues remain to be solved before breath analysis may become a routine cancer screening method. Recently we have shown that with simple modifications, commercial mass spectrometers can sense in real time novel metabolites (e.g. glucose) in breath than previously detected. Here, we propose to employ this technology to compare the breath metabolic profiles of control subjects and cancer patients; and cancer patients before and after tumor removal.The aims are: (i) to advance in the development of alternative analytical platforms in metabolomics, (ii) to increase the knowledge of the still poorly understood underlying mechanisms of lung cancer development and progression and (iii) to determine potential biomarkers in breath of lung cancer patients.