Gliomas Diagnosis, Progress, and Treatment: A Mathematical Approach

The diagnosis and treatment of gliomas continue to pose a significant challenge for oncologists who not only have to contend with managing acute neurological symptoms, but also the almost inevitable development of resistance to treatment. Indeed, the last 25 years have produced minimal advancements in treatment efficacy, even though significant efforts and resources have been invested in the quest for breakthroughs. This effort has not been restricted only to clinicians or oncologists, with mathematical modeling also playing an increasingly important role. The work presented seeks to focus our attention back to the most fundamental question: why are gliomas fatal? Biologically, it is known that glioma lethality is driven by a fast growth that increases intracranial pressure resulting in lethal neurological damage, which current treatments fail to prevent due to tumor cell resistance to treatments such as chemotherapy. The work comprises two main parts: (1) in silico optimization of treatment strategies using chemotherapy coupled with novel cell-repair inhibitors currently in various stages of the clinical trial; and (2) a study of tumor-induced intracranial pressure and edema in gliomas of grade I-IV. Both approaches come together as a first step towards a better understanding of the poor survival rates of patients afflicted with gliomas. They raise new questions about what characterizes the malignancy of primary brain tumors and how clinicians can fight it...