BRIDGE: Brain cancer Research for Innovations and the Development of Glioma Enhanced health care
Target identification and therapeutic development in brain tumors
The human brain remains the least understood organ in biology, and brain disease pose profound challenges, significantly impacting patient quality of life and survival. The BRIDGE initiative aims to address this critical need by leveraging our unique technology for target discovery and enhanced drug delivery in patients with glioblastoma (GBM), the most common and aggressive primary brain tumor. Current standard of care offers no cure with a median overall survival of only ~12 months, underscoring an urgent need for innovative therapies in GBM.
Aims: BRIDGE will unify the expertise of clinicians and basic researchers to tackle key clinical challenges in brain cancer:
1) Identifying effective targets: Over the past decade, we have built a technology platform (featured in e.g., Nature Comm., 2016; PNAS, 2022; Science Transl. Med., 2024) that enables in-depth profiling and discovery of therapeutic targets in patient tumors. This platform opens new avenues for drug development in GBM.
2) Achieving targeted delivery to the brain: The blood-brain barrier (BBB) remains a significant barrier to drug delivery into brain tumors. We aim to develop the use of focused ultrasound - the most promising approach for temporarily opening the BBB - to enhance the precision and efficacy of drug delivery.
Approach: Therapies targeting cell-surface proteins, such as antibody immunotherapies, antibody-drug conjugates, radioimmunotherapy, and CAR-T cell treatments, currently revolutionize cancer care. However, identifying viable cell-surface targets in brain tumors remains a challenge. To address this, we will deploy our in-house developed platform to uncover protein motifs specific to brain tumors. With our pipeline, we can move beyond typical descriptive research to actively validate and screen therapeutic targets using patient-derived tumor models and animal systems.
Our team has identified a lead candidate target in GBM that was recently prioritized for therapeutic development within the national SciLifeLab-drug discovery and development platform. In parallel, we plan to pioneer imaging-guided, low-intensity focused ultrasound in Sweden. By facilitating BBB penetration, FUS may substantially improve the efficacy of GBM treatments, with potential to transform patient outcomes. Further studies will optimize focused ultrasound and explore its synergistic potential with emerging therapeutic approaches.
Expected Outcomes and Clinical Relevance: Our project benefits from state-of-the-art infrastructure for target identification and drug development, alongside clinical expertise to bridge scientific discoveries to clinical applications. Our approach may extend to brain metastases from cancers such as malignant melanoma, lung, and breast, advancing the goal of tumor-agnostic, precision medicine in oncology. Thanks to previous and current funding from FBKS we are now in a position to make significant progress towards transformative treatments of brain tumors.