Project: Integrative Personal Omics Profiles in Glioblastoma Recurrence and Therapy Resistance

Acronym	PerProGlio (Reference Number: ERAPERMED2018-270)
Duration	01/03/2019 - 28/02/2022
Project Topic	Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis and median survival times of < 15 months. Despite multimodal therapy, including surgical resection and radio-chemotherapy, recurrence is common. However, time to recurrence is an individual parameter in patients and depends on genetic factors and on clinical parameters, e.g. extent of resection. In recurrent GBM, repeated surgery can prolong the lifespan if recurrent tumors are detected at early stages. Until now, recurrence monitoring is based on radiologic imaging but suffers from limited sensitivity and confounding effects. Therefore, circulating “liquid biopsy” markers predicting the time window of recurrence are highly desirable. We propose to use our combined expertises of “OMICS” methods to dissect the individual parameters that determine recurrence and therapy resistance in GBM with possible therapeutic implications. Initially, we will use a retrospective cohort of 100 patients with clinical metadata of GBM primary and recurrent samples. Abundance-based biomarkers associated with time-to-recurrence and therapy resistance will be obtained by analysing extracellular vesicles (EVs) with respect to proteolytic fragments (mass spectrometry based), protease activities, and miRNA content. In addition, a full NGS analysis will be performed to characterize recurrence in each individual patient and combine “OMICS” with clinical and imaging data. From these analyses, we propose to identify personalized easy-to-access biopsy markers so that investigation of pre- and post-surgery serum samples (at time of initial surgery) allows to faithful discern tumor-originating molecules through their decreased abundance in post-surgery samples. We further hypothesize that multimodal monitoring, e.g. combining imaging data with molecular markers allows to establish a molecular signature of GBM recurrence which is particularly powerful for reliable prediction of GBM recurrence in a prospective patient cohort.
Network	ERA PerMed
Call	1st Joint Transnational Call for Proposals (2018)

Project partner

Number	Name	Role	Country
1	Philipps Universität Marburg	Coordinator	Germany
2	Albert-Ludwigs Universität Freiburg	Partner	Germany
3	Ospedale San Raffaele Milan	Partner	Italy
4	Hospital Universitario y Politecnico La Fe	Partner	Spain
5	University of Toronto	Partner	Canada
6	Institute of Cellular Biology and Pathology "Nicolae Simionescu"	Partner	Romania