Glioblastoma,a rare,and highly lethal form of brain cancer,poses significant challenges in terms of therapeutic resistance,and poor survival rates for both adult and paediatric patients alike.Despite advancements in b...Glioblastoma,a rare,and highly lethal form of brain cancer,poses significant challenges in terms of therapeutic resistance,and poor survival rates for both adult and paediatric patients alike.Despite advancements in brain cancer research driven by a technological revolution,translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need.This review emphasises the intricate role of receptor tyrosine kinase signalling pathways,epigenetic mechanisms,and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance.We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways.Emerging therapeutic approaches,such as antibody-toxin conjugates or CAR T cell therapies,offer potential by specifically targeting proteins on the glioblastoma cell surface.Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research.Moreover,gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches.Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.展开更多
基金S.A.B.is supported by a Victorian Cancer Agency Mid-Career Research Fellowship(MCRF22003)S.F.is supported by a National Health and Medical Research Council of Australia(NHMRC)Ideas Grant(GNT1184421)+2 种基金R.E.has support from a Cancer Council of Western Australia Research Fellowship and a Brainchild Fellowship from the Pirate Ship FoundationThis work was supported in part through M.RJ,S.A.B.,K.P.,R.E.and,S.F.membership of the Brain Cancer CentreK.P.is supported by an Australian Government Research Training Program Scholarship and the Ann Henderson PhD Scholarship。
文摘Glioblastoma,a rare,and highly lethal form of brain cancer,poses significant challenges in terms of therapeutic resistance,and poor survival rates for both adult and paediatric patients alike.Despite advancements in brain cancer research driven by a technological revolution,translating our understanding of glioblastoma pathogenesis into improved clinical outcomes remains a critical unmet need.This review emphasises the intricate role of receptor tyrosine kinase signalling pathways,epigenetic mechanisms,and metabolic functions in glioblastoma tumourigenesis and therapeutic resistance.We also discuss the extensive efforts over the past two decades that have explored targeted therapies against these pathways.Emerging therapeutic approaches,such as antibody-toxin conjugates or CAR T cell therapies,offer potential by specifically targeting proteins on the glioblastoma cell surface.Combination strategies incorporating protein-targeted therapy and immune-based therapies demonstrate great promise for future clinical research.Moreover,gaining insights into the role of cell-of-origin in glioblastoma treatment response holds the potential to advance precision medicine approaches.Addressing these challenges is crucial to improving outcomes for glioblastoma patients and moving towards more effective precision therapies.
