Abstract
BackgroundGlioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Most patients undergoing radiotherapy, along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after the treatment. We propose to model the pathways active in Glioblastoma using Boolean network techniques. The network captures the genetic interactions and possible mutations that are involved in the development of the brain tumor. The model is used to predict the theoretical efficacies of drugs for the treatment of cancer.ResultsWe use the Boolean network to rank the critical intervention points in the pathway to predict an effective therapeutic strategy for Glioblastoma. Drug repurposing helps to identify non-cancer drugs that could be effective in cancer treatment. We predict the effectiveness of drug combinations of anti-cancer and non-cancer drugs for Glioblastoma.ConclusionsGiven the genetic profile of a GBM tumor, the Boolean model can predict the most effective targets for treatment. We also identified two-drug combinations that could be more effective in killing GBM cells than conventional chemotherapeutic agents. The non-cancer drug Aspirin could potentially increase the cytotoxicity of TMZ in GBM patients.
Highlights
Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments
Biological pathways in glioblastoma To support the design of targeted therapy for Glioblastoma Multiforme (GBM), it is necessary to model the cell signaling pathways involved in the development of cancer
Genes associated with the Fas pathway that is responsible for extrinsic apoptosis, are a feature of GBM tumors
Summary
Glioblastoma Multiforme, an aggressive primary brain tumor, has a poor prognosis and no effective standard of care treatments. Along with Temozolomide chemotherapy, develop resistance to the drug, and recurrence of the tumor is a common issue after the treatment. Current standard of care (SOC) treatments for GBM include maximum safe surgical resection, radiation, temozolomide (TMZ) chemotherapy and recently FDA approved tumor treating fields (Optune) for newly diagnosed patients as well as bevacizumab (Avastin) for recurrent disease [2, 3]. GBM still stays as one of the most challenging cancers to treat due to its complexity or tumor heterogeneity, infiltrative nature and low efficacy of current treatment modalities which results in short-term survival rate. A few of the main challenges to GBM treatment are resistance to temozolomide and recurrence of cancer after radiation therapy. By prioritizing the key genetic targets involved in the progression of GBM, the best drug combination can be predicted
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