Roles of the Polyphosphate/ Factor XII- pathway in malignancy-associated inflammatory and prothrombotic diseases: New biomarkers and therapeutic drug targets.

• Applicant: Dr. Verena Kiencke
• Subject Area: Public Health, Healthcare Research, Social and Occupational Medicine
• Term: from 2017 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 391039554

Cancer induces a thrombo-inflammatory state and vice versa thrombosis and inflammation contribute to cancer growth. Today, the causal relationship between inflammation, coagulation and cancer is widely accepted; however, many of the molecular and cellular mechanisms mediating this relationship have remained enigmatic. Coagulation factor XII (FXII, Hageman factor) and its activator polyphosphate (polyP) have a central role for thrombosis, promote cell-proliferation and induce proinflammatory reactions. The goal of this proposal is to analyze mechanisms, diagnostic application and therapeutic implications of the polyP/FXII pathway in cancer. We aim to analyse (1) the role of the polyP/FXII-pathway for tumor growth and tumor associated proinflammatory and procoagulant mechanisms, (2) establish polyP as a prognostic biomarker for assessment of inflammation and coagulation, and (3) develop polyP/FXII-based therapies for interference with inflammatory and procoagulant reactions and tumor growth in cancer patients. The translational project comprises molecular biology, cell biology, advanced diagnostics, genetically altered animal models and patient materials to explore impact of polyP and FXII for malignant diseases.A comprehensive insight into the functions of the polyP/FXII axis in cancer offers a novel and unique opportunity for development of predictive tumor and thrombosis biomarkers and improved patient care by establishing a safe anticoagulation therapy with additional anti-inflammatory and anti-mitogenic activities.

• DFG Programme: Research Grants