Potentiation of Chemotherapy in Brain Tumors by Zinc

Glioblastoma (GB) is the most common and aggressive type of primary malignant brain tumor in adults. Despite advances in surgical resection, radiotherapy and chemotherapy, prognosis remains very poor. Temozolomide (TMZ) as an alkylating agent has become part of GBM management but it has contributed only marginally to prolongation of life in GBM patients. Our aim is to evaluate the therapeutic potential of the trace element zinc to facilitate temozolomide tumor cell toxicity in GBM. P53 gene is inactive/mutant in most of these patients which may affect the resistance to apoptosis of tumor cells by chemotherapy. Zinc (Zn) has a crucial role in the biology of p53, in that p53 binds to DNA through a structurally complex domain stabilized by zinc atom. We have shown that the cytotoxic activity of TMZ is substantially increased with the addition of zinc in vitro with GBM cell lines as well as in vivo, with intracranial GBM xenografts. Numerous studies of zinc in animal models and in human subjects support its use in the treatment and possibly the prevention of cancer. Zinc has been consumed by the public as an essential mineral (and thus is category A drug) in concentrations which allows this effect with Temozolomide. Vitamin C could add to this by priming the immune system for lymphocyte- linked cancer killing. The vitamin c increases the number of tumor infiltrating lymphocytes and enhances the activation of the immune system.We propose a single arm phase II clinical trial in 30 newly diagnosed GBM patients who will be treated with the standard chemo-radiotherapy with the addition of zinc and vitamin C.