The PROVABES network is funded by the Federal Ministry of Education and Research Germany - BMBF
PROspective VAlidation of Biomarkers in Ewing Sarcoma
for personalised translational medicine
PROVABES is a joint proposal of the three leading European Ewing sarcoma study groups: EURO-EWING, the Italian Sarcoma Group (ISG) and the Spanish Sarcoma Group (GEIS).
These groups have formed a consortium for collaborating with the leading experts on molecular, cellular and translational Ewing sarcoma (ES) research. Each of these scientists will contribute his or her unique expertise to the validation of prognostically relevant biomarkers of solid tumours.
The majority of European ES patients are treated within clinical trials under the auspices of the clinical trial groups cooperating in this consortium. Owing to multimodal treatment concepts, two-thirds of the patients with localised disease achieve sustained remission; still, approximately 30 % relapse. While clinical prognostic markers such as primary dissemination, tumour site, tumour size, patient`s age and histological response to chemotherapy are established and used for therapeutic stratification, little is known about biological factors that determine the risk of relapse or progression and thus might help to differentiate patients at risk from those eligible for less intense treatment.
Prospectively validated biomarkers are thus needed to provide personalised risk-adapted therapeutic approaches.
ES was the first solid malignancy defined by the presence of tumour-specific EWS-ETS gene fusions, mainly EWSR1-FLI1 translocations.
Secondary genetic alterations have emerged as candidates to account for the most aggressive forms of ES, and might serve as predictive biomarkers.
The consortium has an outstanding experience in translational Ewing Sarcoma research. We have recently detected a number of promising biomarkers. It is expected that not one single biomarker but a combination of markers will provide the most informative prognostic algorithm for patients with ES.
PROVABES will validate selected biomarkers prospectively on all levels of cell biology: Genom, Transcriptom and Proteom. These studies will be complemented by studies of circulation biomarkers. In a separate work package, the functional in vitro validation and interaction of selected biomarkers will be tested.