Investigating Glioblastoma Growth and Metabolism via MNK-eIF4E Pathway Modulation using NMR Spectroscopy*

Glioblastoma multiforme is among the most aggressive and deadliest forms of cancer. The current treatment approach involves surgery to remove the tumor, followed by radiation therapy and supplementary chemotherapy. Temozolomide (TMZ) is the established standard for chemotherapy. Nevertheless, complete eradication of the tumor is often not achievable, leading to recurrences. Studies have revealed that temozolomide activates the MNK ½ pathway, leading to the phosphorylation of eukaryotic initiation factor 4E (eIF4E), a factor implicated in cancer progression. Higher temozolomide dosages can result in increased toxicity, with some patients experiencing neuropathic pain. Tomivosertib (eFT508) is an inhibitor of MNK ½ that has demonstrated the ability to target eIF4E phosphorylation and the generation of reactive oxygen species (ROS) in chemotherapy-induced neuropathy. This research seeks to investigate the effectiveness of concurrently administering temozolomide and tomivosertib in hindering the metabolism and proliferation of glioblastoma. The study will include the presentation and discussion of data obtained from NMR spectroscopy and other relevant sources.