Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

ABSTRACT: Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ

SUBMITTER: Monteiro C 

PROVIDER: S-EPMC9018424 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature