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Frontiers in Mathematical Oncology

The Brain Tumor Problem

Mark Gilbert

National Institutes of Health


Primary brain and spinal cord tumors are the most common and lethal cancers in children, and remain among the most lethal adult cancers despite their lower incidence compared to other common cancers.  Although there have been many advances in neurosurgery, radiation oncology, and imaging of the nervous system, the treatments for patients with malignant brain and spinal cord tumors rarely result in a cure. The reasons can be attributed to a number of factors, including the vast molecular heterogeneity of the tumors, the unique microenvironment and immunologic background, and the difficulty in obtaining spatial and longitudinal tumor data. Some tumors, like Glioblastomas, present great inter and intra tumor molecular heterogeneity and their aggressiveness can be contributed to a large mutation burden as well as other alterations in cellular biology. In contrast, other tumors, like Atypical Teratoid Rhabdoid Tumors, are rarely mutated, and yet display an aggressive behavior that is the result of distinct epigenetic modifications. The unique microenvironment of these tumors makes it hard to create laboratory models that recapitulate the disease sufficiently, and biological barriers (like the Blood Brain Barrier) make repurposing of therapies that are effective in other cancers difficult. Despite these challenges, the accumulation of big data through projects like The Cancer Genome Atlas has revolutionized classification of these tumors based on molecular features, and provides unique opportunities in our search for new therapeutics. At the Neuro-Oncology Branch we are developing an integrated clinical, translational, and basic research with an important informatics component focused on integration of genetic and clinical data, enabling rational selection of preclinical models, and construction of computational models of the impacted biological pathways.  The work was done jointly with Orieta Celiku.