A systematic computational analysis of the endosomal recycling pathway in glioblastoma

Abstract

Abstract Purpose Glioblastoma (GBM) is the most common and most aggressive brain cancer in adults. Approximately 250,000 new cases are diagnosed worldwide per year, and its incidence is rising due to our aging population. The standard treatment is brutal and has not changed in 20 years, and more than 85% of patients will die within two years of their diagnosis. There is thus an urgent need to identify new drug targets and develop novel therapeutic strategies that will increase survival and improve quality of life. Methods Using publicly available genomics, transcriptomics and proteomics datasets, we show that key regulators of endosomal recycling are dysregulated in GBM and are linked to survival outcomes. Results We report here that an intracellular membrane trafficking pathway called the endosomal recycling pathway represents a novel target that could be exploited for the development of small molecule inhibitors to treat people with GBM. We report an 8-gene endosomal recycling prognostic signature that can distinguish low-risk from high-risk GBM and potentially identify tumours that may benefit from endosomal recycling inhibitors. Conclusion This study presents the first systematic analysis of the endosomal recycling pathway in glioblastoma and proposes that it is a promising target for the development of novel therapies and therapeutic strategies that could improve the outcomes for patients with glioblastoma.