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Natural sciences
- Analytical separation and detection techniques
- Biogeochemistry
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Medical and health sciences
- Regulation of metabolism
- Cancer diagnosis
Chemotherapy using Pt-based compounds is a standard cancer treatment, but tumours may develop chemoresistance, resulting in treatment failure. One mechanism behind chemoresistance is the disruption of metal homeostasis, which relates to changes in metal-binding proteins and redox status. The altered expression of ion channels (for Ca, K, and Mg) and Cu-, Fe-, and Zn-binding proteins has already been associated with resistance to chemotherapeutic drugs. This project will investigate the link between the essential mineral elements Ca, Cu, Fe, K, Mg, and Zn and chemosensitivity/resistance in high-grade serous ovarian cancer (HGSOC) using elemental and isotopic analysis (isotope ratios can signal biochemical changes in cases where element concentrations are not affected yet). Methods will be developed to isolate target elements from the sample matrix (including exogenous Pt) prior to analysis and reference materials will be isotopically characterised to validate results. This research will assess (i) changes to metal homeostasis in chemoresistant HGSOC cell lines and tumour spheroids; (ii) the isotopic variability within HGSOC patients and the potential link with disease severity; (iii) the potential of isotope ratios as prognostic and/or predictive biomarker, with the final aim of improving patient survival rate and predicting response towards chemotherapeutic treatment.