Biomarkers of tumor recurrence in pancreatic cancer
Pancreatic cancer has the worst prognosis of all solid tumors with 5-year survival rates < 5%. Surgical resection of early stage tumors to date offers the only hope for potentially curative treatment. However, local and/or distant tumor recurrence is a frequent event even after R0 resection, thus current guidelines recommend adjuvant chemotherapy that has been shown to double 5-year-survival rates for these patients (20.7% vs 10.4%). Even so, recurrence is still the most common course of the disease, and no standard means for diagnosis and treatment of early recurrence are established yet. The development of novel approaches for postoperative monitoring of resected patients to detect recurrence at an early time point would thus address an unmet clinical need that would be a key factor in increasing survival and quality of life in these patients. Members of this consortium have previously identified a panel of diagnostic mRNA and miRNA markers and have designed the prototype of a diagnostic tool utilizing the TaqMan Array technology. The aim of this proposal is to i) additionally incorporate detection of pancreatic cancer-associated genomic mutations in the biomarker array, and to ii) validate the pancreatic cancer TaqMan array through different stages of technical and early clinical validation in the setting of PDAC patients resected with curative intent. The final goal is to develop a diagnostic tool to be used during follow-up of resected patients for the early, accurate and non-invasive detection of systemic markers of recurrence at a stage when it is not yet detectable by imaging. To technically validate the biomarker array, we will analyze “liquid biopsies” (serum, urine) of patients from existing collections and case/control studies which are stored in quality assured biobanks in the consortium. In the second stage of the project, the diagnostic performance of the biomarker TaqMan array will be rigorously validated using patient samples prospectively collected within the project at different time points after R0 resection of pancreatic cancer. The consortium comprises clinical partners in leading European centers with extensive experience in the management of pancreatic cancer patients as well as pancreatic cancer molecular biology and biomarker discovery. Moreover, existing collaborations with industrial partners will be instrumental in translating the scientific results into marketable clinical applications.
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This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement No. 964264.