ArticleCell death & disease2025
LMNA-PRKDC axis enhances DNA repair and promotes chemoresistance in glioblastoma.
Article in Cell death & disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed.
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Targeting replication stress in glioblastoma: From genotoxic treatment and inhibitors of the DNA damage response to immunotherapy.Neuro-oncology advancesReview
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Authors and funding
15 authors.
Funding
Abstract
Glioblastoma (GBM) remains one of the deadliest primary brain tumors, with rapid recurrence and near-universal resistance to temozolomide (TMZ) limiting long-term survival. In this study, we identify a clinically actionable mechanism of resistance driven by the LMNA-PRKDC axis, which enhances DNA repair and tumor cell survival following TMZ treatment. Using patient-derived xenograft models of recurrent GBM, we demonstrate that resistant tumors exhibit elevated LMNA expression and increased physical interaction with PRKDC, a central regulator of non-homologous end joining (NHEJ). This interaction accelerates the repair of TMZ-induced DNA lesions, contributing to therapeutic failure. Proteomic profiling and targeted immunoprecipitation revealed a distinct LMNA-PRKDC-associated DNA repair complex. Inhibition of PRKDC with the ATP-competitive inhibitor KU57788 reversed resistance, restoring TMZ sensitivity and impairing tumor growth in vivo. Single-cell RNA sequencing of primary and recurrent GBM specimens further identified LMNA-PRKDC co-expression as a hallmark of treatment-resistant, glioma stem-like cell populations. Importantly, high LMNA-PRKDC expression was associated with inferior survival outcomes in GBM patient cohorts. These results establish the LMNA-PRKDC axis as a functional driver of TMZ resistance through enhanced DNA repair capacity in stem-like tumor subpopulations. Our findings support pharmacologic inhibition of PRKDC as a rational strategy to resensitize resistant GBM to standard chemotherapy and offer a foundation for future biomarker-driven clinical trials targeting DNA repair vulnerabilities in recurrent disease.
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Registered trials
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