Targeting the NF-kB and MGMT Pathways to Treat Newly Diagnosed Glioblastoma
Background
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive and common malignant primary brain tumors in adults. GBM develops from the lineage of star-shaped glial cells, called astrocytes, that support nerve cells, hence the classification of glioblastoma as a Grade IV (most serious) astrocytoma. Current barriers to successful treatment include their complex tumor heterogeneity, diffuse invasiveness, and the presence of a subpopulation of glioma cells with stem-like properties, thus termed brain tumor–initiating cells (BTIC), that have been shown to confer resistance to conventional therapies, such as radio and chemotherapies. As a result, patient prognosis is currently at 14.6 months.
Purpose
The purpose of this investigation is to test what combination and dosage of zinc, disulfiram, and temozolomide will therapeutically enhance treatments for newly diagnosed glioblastoma. Since many of the current therapies are ineffective towards glioblastoma, and patient prognosis continues to be disappointing, finding new methods to treat this brain tumor is of increasing concern. The investigation also aims to develop a treatment that is more cost effective, hence the usage of repositioned drugs (zinc and disulfiram) to determine if temozolomide will be therapeutically enhanced. Currently, higher end therapeutical treatments such as gene therapy and immunotherapy are financially crippling: Immunotherapy costs upwards of $100,000 per year while gene therapy costs between $500,000 to $1,500,000 per year. As the average American salary is $74,000, developing a cost effective treatment is critical.
Hypotheses
If drug combinations are introduced to newly diagnosed glioblastoma, then the drug cytotoxicity will exponentially increase as the days prolong.
​
If temozolomide is used alone or in combination with zinc and disulfiram, then temozolomide and disulfiram by itself will be the least effective treatment.
​
If temozolomide is used alone or in combination with zinc and disulfiram, then combinations that include zinc will be most effective in inhibiting the NF-kB and MGMT pathways in newly diagnosed glioblastoma.