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

Brittany Dewdney, Misty R. Jenkins, Sarah A. Best, Saskia Freytag, Krishneel Prasad, Jeff Holst, Raelene Endersby, Terrance G. Johns

Research output: Contribution to journalReview articlepeer-review

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number400
Number of pages33
JournalSignal Transduction and Targeted Therapy
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 2023

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