Axonal injury is a targetable driver of glioblastoma progression.

ABSTRACT: Glioblastoma (GBM) is an aggressive and highly therapy-resistant brain tumour^1,2. Although advanced disease has been intensely investigated, the mechanisms that underpin the earlier, likely more tractable, stages of GBM development remain poorly understood. Here we identify axonal injury as a key driver of GBM progression, which we find is induced in white matter by early tumour cells preferentially expanding in this region. Mechanistically, axonal injury promotes gliomagenesis by triggering Wallerian degeneration, a targetable active programme of axonal death³, which we show increases neuroinflammation and tumour proliferation. Inactivation of SARM1, the key enzyme activated in response to injury that mediates Wallerian degeneration⁴, was sufficient to bre

SUBMITTER: Clements M 

PROVIDER: S-EPMC12507684 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature