CUTLINE: A team of physicians and neuroscientists from Dartmouth, Harvard and Georgetown University have uncovered the biological basis for fluorescence in fluorescence-guided neurosurgery providing a potential pathway to maximize the effectiveness of surgery for brain tumors.
SUMMARY: Despite optimal medical management, aggressive brain cancers, like Glioblastoma multiforme (GBM) tend to be lethal. One of the most effective medical interventions for this type of cancer is surgery. Maximizing the extent of the surgical resection of these tumors improve survival significantly, unfortunately the surgeon’s ability to achieve good resection is challenged by the lack of obvious tumor borders. This study unveils the gene expression pattern that allows brain tumors to ‘glow’ when treated with 5-aminolevulinic acid, providing a basis to identify novel strategies to maximize the effectiveness of brain tumor surgery, and improve patient survival.
LEBANON, NH - GBM is one the most aggressive brain tumors with one of the worst survival rates of all cancers. Maximizing the extent of tumor extracted during surgery has been important to improve survival. Unfortunately, the surgeon’s ability to do this is challenged by the lack of obvious tumor borders in this tumor type. Fluorescence-guided neurosurgery with 5-aminolevulinic acid (5-ALA) improves GBM resection significantly by literally making tumor tissue glow. However, the effectiveness of this promising state-of-the-art technique is limited by the fact that not all brain tumor tissues fluoresce with 5-ALA.
To begin solving this problem, Dr. Damian A. Almiron-Bonnin and his team studied the bio-molecular distinctions between brain tumor tissues that fluoresce and brain tumor tissues that do not fluoresce after 5-ALA administration. Dr. Almiron-Bonnin et al. recently published a study where they successfully identify the gene expression patterns that allow some brain tumor tissues to ‘glow’ during fluorescence-guided neurosurgery. This study shows that the gene expression of fluorescent and non-fluorescent tumors is profoundly different, and are associated with distinct cellular functions and different biological pathways. The research team behind this study was integrated by leaders in the field of GBM research including Dr. David W. Roberts, Dr. Brian W. Pogue, Dr. Linton Evans, Dr. Pablo Valdes, and Dr. Mark Israel.
“This discovery does not only provide a basis to identify novel strategies to maximize the effectiveness of fluorescence –guided neurosurgery, but it also offers an approach to screen patients that would benefit the most from this technique” says Dr. Almiron-Bonnin. “This knowledge could potentially improve .” The team’s work was recently published in the prestigious Journal of Neuro-Oncology: Characterizing the heterogeneity in 5-aminolevulinic acid–induced fluorescence in glioblastoma.
“These brain tumors are the most aggressive and common non-metastatic brain tumors in adults and children. Currently, there is no curative therapy, and consequently, brain tumors are responsible for about a fourth of all cancer-related deaths in children and young adults.” says Dr. Almiron-Bonnin. “Our team is constantly trying to improve our understanding of these tumors in order to improve patient care.”
Looking ahead, the team hopes to improve the efficacy of fluorescent-guided neurosurgery by exploring combinations of different fluorescent agents (such as quantum dot nanoparticles, or antibody-bound agents) to target cancer tissues with different molecular properties.
About Norris Cotton Cancer Center at Dartmouth-Hitchcock
Norris Cotton Cancer Center combines advanced cancer research at Dartmouth’s Geisel School of Medicine with patient-centered cancer care provided at Dartmouth-Hitchcock Medical Center in Lebanon, NH, at Dartmouth-Hitchcock regional locations in Manchester, Nashua and Keene, NH, and St. Johnsbury, VT, and at partner hospitals throughout New Hampshire and Vermont. It is one of 49 centers nationwide to earn the National Cancer Institute’s “Comprehensive Cancer Center” designation. Learn more about Norris Cotton Cancer Center research, programs, and clinical trials online at cancer.dartmouth.edu.