NMR Studies of Glucose Metabolism after Temozolomide Administration in Glioblastoma in vitro

Glioblastoma multiforme (GBM) is an aggressive type of brain cancer with a high recurrence rate despite medical advancements. The current gold standard chemotherapeutic treatment after tumor resection is Temozolomide (TMZ), which induces DNA damage, killing tumor cells. It remains the primary drug for GBM due to its effective penetration of the blood-brain barrier, but it still fails to boost survival beyond five years. Hence, an alternative pathway as a novel target to improve the treatment's efficacy may address this problem. Studies have shown that a pathway called MNK-eIF4E promotes the proliferation of brain cancer and induces chemotherapy-induced neuropathic pain in other types of cancer. Results showed that the MNK inhibitor, eFT508, significantly decreased eIF4e phosphorylation and proliferation of GBM cells after concurrent administration with TMZ. Moreover, there was no significant difference among the metabolites upon drug administration, but an unknown metabolite appeared upon TMZ administration. We hypothesized that this unknown metabolite is GABA— a possible additional target in glioblastoma. Recent studies showed that GABA signaling in other types of cancer promotes proliferation; hence, we aim to validate the identity of this metabolite. These preliminary NMR results will be discussed along with other supporting data.