From signalling pathways to targeted therapies: unravelling glioblastoma’s secrets and harnessing two decades of progress  

作　　者：Brittany Dewdney Misty RJenkins Sarah ABest Saskia Freytag Krishneel Prasad Jeff Holst Raelene Endersby Terrance GJohns 

机构地区：[1]Cancer Centre,Telethon Kids Institute,Nedlands,WA,6009,Australia [2]Centre For Child Health Research,University of Western Australia,Perth,WA,6009,Australia [3]Immunology Division,The Walter and Eliza Hall Institute of Medical Research,Melbourne,3052,Australia [4]Department of Medical Biology,University of Melbourne,Melbourne,3010,Australia [5]Personalised Oncology Division,The Walter and Eliza Hall Institute of Medical Research,Melbourne,3052,Australia [6]School of Biomedical Sciences,University of New South Wales,Sydney,2052,Australia

出　　处：《Signal Transduction and Targeted Therapy》2023年第11期5270-5302,共33页信号转导与靶向治疗（英文）

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);R.E.has support from a Cancer Council of Western Australia Research Fellowship and a Brainchild Fellowship from the Pirate Ship Foundation;This work was supported in part through M.RJ,S.A.B.,K.P.,R.E.and,S.F.membership of the Brain Cancer Centre;K.P.is supported by an Australian Government Research Training Program Scholarship and the Ann Henderson PhD Scholarship。

摘　　要：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.

关 键 词：GLIOBLASTOMA THERAPIES TARGETED 

分 类 号：R730.5[医药卫生—肿瘤]