Trace metals disorder as biomarker in biliary tract cancers

Trace metals disorder MD in the body of cancer patients is associated with health problems for which treatments are poorly effective. In this project, we set to identify and investigate the MD in biliary tract cancers at pre-clinical and clinical level by integrating inductively coupled plasma mass spectrometry (ICP-MS) methods into analytical methodology to test the main hypothesis that MD can be used as biomarkers for disease. Objectives will be met by the development and the application of newly developed analytical methods to metal-based biomarker research in oncology at pre-clinical and clinical level. Clinical study is designed with the aim to identify serum Cu, Zn and Fe levels and ratios, and Cu speciation and isotopic fractionation as a predictive biomarker of response to systemic therapy in correlation with radiological CT evaluation for response to systemic therapy and thereby confirm the feasibility of the approach proposed. Project consist of 4 work packages. Within WP1, protocols for sample collection, selection, storage and preparation (3D models, tissue, cells, and plasma/serum) will be selected. Special attention will be paid to preserve the chemical species analysed integrity. These include also preparation and characterisation of calibrants, isotopic standards, model samples and reference test materials. WP 2 is devoted to the developments and applications of ICP-MS based analytical methods (total metal concentration, speciation and isotopic fractionation analysis) for the identification of MD and altered speciation and isotopic ratios of essential trace elements (mainly Cu, then Zn and Fe) in the investigation on the possibility to use MD as bio-marker of biliary tract cancers. Additionally, methods for the determination of the quantitative distribution of the selected cancer-related analytes (including possible biomarkers) relevant for disease diagnosis and treatment in tumour spheroid (3D model) at the low ng/g concentration level by laser ablation – ICP-MS and supporting imaging techniques for possible future application at the clinical level (cancer biopsy samples) will be develop and validate and single cell ICP-MS technique introduced to pre-clinical investigation for the correlation of individual cell metal content with other important biochemical parameters to predict the response of tumour in cancer therapy. WP3 is a prospective, non-interventional, non-randomised clinical trial with 20 patients and 20 healthy volunteers carefully prepared to identify serum Cu levels, its speciation and/or isotopic fractionation as a predictive biomarker of response to systemic therapy in correlation with radiological CT evaluation for response to systemic therapy. With this, newly developed analytical methods based on ICP-MS will be directly integrated to metal-based biomarker research in oncology. Statistical data handling is part of all the experimental WPs (1 to 3), while WP4 is devoted to management (Creating impact, management and coordination). Such organisation of the project is optimal for the number of partners participating, experimental work planed and amount of finance. Topic of this project is oriented to the needs of end-users. The beneficiaries from the results of this project will include academics, health protection bodies and clinics, clinical laboratories, oncological patients and wider human society.