Ara-C suppresses H3 K27-altered spinal cord diffuse midline glioma growth and enhances immune checkpoint blockade sensitivity.

ABSTRACT: H3 K27-altered spinal cord diffuse midline glioma (H3-SCDMG) poses therapeutic challenges. Analysis of 73 clinical samples revealed heightened proliferation in H3-SCDMG versus wild-type tumors, suggesting therapeutic vulnerabilities. Drug screening identified cytarabine (Ara-C) as highly effective in inhibiting proliferation in H3 K27M cell models, recently established patient-derived cells, and patient-derived xenograft models. Mechanistically, Ara-C can suppress tumor growth through DNA damage, cell-cycle arrest, and apoptosis. An investigator-initiated clinical trial involving four patients showed benefits in three cases. In addition, a subset of cells exhibited senescence and senescence-associated secretory phenotype post-Ara-C treatment, accompanied by several immune checkpoint ligand

SUBMITTER: Pang B 

PROVIDER: S-EPMC12002095 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature