Personalized targeted glioblastoma therapies by ex vivo drug screening: Advanced brain Tumour TheRApy Clinical Trial (ATTRACT)

Programme

Clinical research group

Project coordination

Medical University of Vienna; Assoc.-Prof. PD Dr. Anna Sophie Berghoff

Project partners

• Danube Private University
• CBmed GmbH
• Medizinische Universität Graz
• Kepler Universitätsklinikum/Johannes Kepler Universität
• Karl Landsteiner Universität für Gesundheitswissenschaften
• Medizinische Universität Innsbruck 
• Austrian Institute of Technology (AIT)

Researchers involved at DPU

Univ.-Prof. Priv.-Doz. Dr. Julia Furtner-Srajer, PhD, MBA

Abstract

Glioblastomas are the most common malignant brain tumors in adults. They are considered highly aggressive, are associated with a substantial burden for affected patients, and continue to have a very poor prognosis despite extensive research efforts. A major reason for this is that many drugs only reach the brain to a limited extent, and the tumor shows pronounced resistance to a wide range of therapeutic agents. In approximately 60–70% of patients, the MGMT gene promoter is unmethylated, which further reduces treatment efficacy and worsens prognosis. There is therefore an urgent need for individually tailored treatment approaches.

The ATTRACT project aims to establish the concept of functional precision medicine—identifying, for each individual patient, the drugs that are most effective against their specific tumor. This is made possible through an interdisciplinary Austrian consortium building on the long-standing expertise of neuro-oncological centers as well as leading basic and translational research institutions.

A central first step is the establishment of an Austria-wide glioblastoma biobank. Several clinical centers—including Vienna (AKH Wien, Klinik Donaustadt and Klinik Landstraße), Graz, St. Pölten, Linz, Innsbruck, Wiener Neustadt, Klagenfurt, Salzburg, and Feldkirch—will enroll patients and collect biological material. Within four years, approximately 800 adults (aged 18 and older) with radiological suspicion of glioblastoma are expected to be included in the biobank. At diagnosis and, if applicable, at recurrence, tumor tissue and blood samples will be collected. From fresh tumor tissue, patient-derived cell cultures (PDCs) will be established and subsequently used in a drug sensitivity testing platform. This platform assesses how each tumor responds to a selected panel of therapeutic agents. If sufficient tissue is available, additional samples will be cryopreserved for future research projects.

The clinical benefit of this approach will be evaluated in a study involving 240 adults with newly diagnosed glioblastoma and an unmethylated MGMT promoter. Participants will be randomly assigned to one of two groups: a standard group receiving conventional histological analysis, and an intervention group in which additional PDC-based drug screening is performed. Based on these results, a molecular tumor board—including the local principal investigator and the treating physician—will develop a personalized treatment recommendation. The treating physician will then discuss this recommendation with the patient, who may choose whether it should be implemented within a “Named Patient Program.”

Using the biobank, treatment response and resistance mechanisms will be investigated through molecular biological analyses of PDCs and tumor tissue. These data will be integrated with imaging findings and clinical information. An integrative analysis approach, including artificial intelligence methods, will be applied to identify novel biomarkers. In this way, ATTRACT provides comprehensive insights into glioblastoma biology and lays the foundation for the development of innovative and more effective therapeutic strategies.

Read more about the project