MEK Inhibition in Glioblastoma: Current Perspectives and Future Directions

The Mitogen-activated protein kinase kinase (MEK) protein family has dual-specificity protein kinases with a myriad of cellular functions that include but are not limited to cell survival, cell division, immunologic response, angiogenesis, and cellular senescence. MEK is crucial in the MAPK signaling pathway, regulating different organ systems, including the CNS. Increased activation and dysregulation of the MEK pathway is reportedly observed in 30% of all malignancies. The diversity of MEK renders it a prime target for inhibition in treating cancer. MEK inhibition has been studied in the context of melanoma, non-small cell lung cancer, breast cancer, and colorectal cancer, among others. The standard treatment for glioblastoma (resection, temozolomide, and radiation) remains relatively futile, which warrants alternative treatment options. Therefore, MEK inhibition has garnered more attention in recent years as investigators have explored its role in treating the most aggressive and most common primary brain tumor, glioblastoma. MEK inhibitors have shown efficacy in pre-clinical investigations as well as some promise in clinical trials which have demonstrated improved overall and progression-free survival. This underscores the potential of MEK inhibition in glioblastoma therapy and represents an area that likely warrants further research. However, there are few comprehensive and unifying reviews discussing the current state of MEK inhibition in glioblastoma therapy. We begin this review by detailing the normal function of MEK as it pertains to the CNS. We then compiled relevant pre-clinical and clinical studies to investigate recent research discussing the role of MEK inhibition in glioblastoma therapy.