Wellcome Trust Joint Basic and Clinical PhD Programme at the Institute of Cancer Research: 'Study of biomarkers in solid tumours including malignant melanoma and colon carcinoma by LC-MS metabonomics'. (360G-Wellcome-090952_Z_09_Z)

Reversed-phased Ultra-Performance Liquid Chromatography (RP-UPLC)-Quadropole Time-of-Flight (QTOF) mass spectroscopy (MS) metabonomics offers high levels of resolution, sensitivity and speed as a novel and promising approach to study circulating biomarkers. A reproducible LC-MS metabonomic signature of a human melanoma cell line has been observed in-vitro and this has been further validated in vivo in the plasma of mice bearing human tumour xenografts (unpublished observation). The aim of the project is to discover novel metabonomic signatures of solid tumours with a particular focus on the correlation of these with particular malignancies (e.g. melanoma and colorectal cancers) and signal transduction aberrations (e.g. MAPK and PI3K pathways) by RP-UPLC-QTOF-MS using a combination of in vitro cell line models and in vivo human xenograft models, additionally examining the impact of the adminstration of specific inhibitors of target molecule(s) that mediate key signal transduction pathways. If robust LC-MS signatures are reliably identified and validated in pre-clinical models, correlations in clinical specimens will subsequently be pursued. Formal analytical methodologies, including functional group derivatisation and tandem MS, will also be employed to deconvolute the LC-MS signatures alongside the use of online databases (e.g. HMDB and METLIN) to better understand the underlying biological significance of our findings.