Our studies are focused on but not limited to primary brain tumors, which integrates well with the PI’s clinical proficiency as a consultant Neuro-oncologist.
Although the overall mortality in cancer is steadily decreasing, major groups of patients with malignant tumors of e.g. the brain, pancreas, and lung still respond poorly to available treatments and have a dismal prognosis. The key clinical challenge addressed by our group relates to the inherent adaptive capacity of tumors, resulting in resistance to conventional oncological treatments, but that also offers new avenues for therapeutic intervention. The overarching goal of our studies is to provide new strategies for the treatment and diagnosis of cancer based on recent, original findings by our group. We use a translational approach encompassing internationally unique patient materials from randomized clinical trials and population based studies combined with recently established cutting edge analytical platforms.
- Novel role for lipoproteins and extracellular vesicles as signalosomes and nutrients in the glioma tumor microenvironment
- Finding the targets - antigens of the stressed tumor niche
- Metabolic rewiring of immune cells in glioma
In these studies, we ask provocative questions about, and challenge the current perception of how tumor cells receive and transfer complex biological information. Our recent studies have provided novel insights into the central role of lipoproteins and extracellular vesicles (EVs) in cancer, and the utility of EVs in non-invasive diagnosis of brain tumors (e.g. Kucharzewska, et al., PNAS, 2013; Christianson, et al., PNAS, 2013; Menard, et al., Cancer Res, 2016; Indira Chandran, et al., Clin Cancer Res, 2019). Ongoing studies will elucidate how glioma cells fuel their increased metabolic demands through increased recruitment and storage of EVs and lipoproteins.
The concept of antibody-drug conjugate (ADC)-based treatment has entered the clinic with approval in the treatment of breast cancer and lymphoma, and more than 60 ADCs are currently tested in clinical trials, including in glioma. However, the identification of internalizing surface antigens for specific drug targeting of tumor cells remains a challenge of high clinical relevance. We have developed a new method for functional mapping of the cancer cell-surface proteome, and recently revealed that stress adaptation modulates the global membrane proteome (Bourseau-Guilmain, et al., 2016). This unique approach is applied for the identification and targeting of novel tumor antigens of the treatment-resistant tumor niche.
Ongoing studies have identified novel, and potentially targetable immune cell entities in the tumor microenvironment, suggesting myeloid cell (TAN and TAM) metabolic polarization into a pro-malignant state. Detailed functional and molecular profiling of specific stromal and immune cell populations will provide novel insights on the immunobiology of GBM, and may reveal underlying immunosuppressive mechanisms paving the way towards innovative therapeutic approaches.