ArticleJCO precision oncology2025
Synthetic Lethal Co-Mutations in DNA Damage Response Pathways Predict Response to Immunotherapy in Pan-Cancer.
Article in JCO precision oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Synthetic lethality between PBRM1 deficiency and PARP inhibitors: exploiting G2/M checkpoint arrest in colorectal cancer.Molecular medicine (Cambridge, Mass.) · 2026Article
- Integrating molecular targeting and immune modulation in triple-negative breast cancer: from mechanistic insights to therapeutic innovation.Frontiers in immunology · 2025Review
- The DDR-immune fitness score: a biomarker for guiding parp and immunotherapy synergy in extensive-stage small cell lung cancer.Frontiers in oncology · 2025Review
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDespite the significance of immune checkpoint inhibitors (ICIs) in solid tumor treatment, identifying ICI-sensitive populations remains a challenge. Mutations in DNA damage response (DDR) pathway genes are increasingly linked to favorable ICI responses; however, selection criteria for specific DDR pathway biomarkers remain elusive.
methodsData of patients with cancer who received ICIs and non-ICI therapy were extracted from public databases. Synthetic lethal (SL) gene combinations were selected from the SynLethDB database. Kaplan-Meier analysis was conducted to investigate the correlation between SL gene co-mutations in DDR pathways and prognosis. Immune infiltration analysis was performed using the Timer online tool based on DNA and RNA sequences obtained from The Cancer Genome Atlas database.
resultsPatients with synthetic lethal co-mutations in DDR pathways exhibited significantly extended overall survival (HRhazard ratio [HR], 0.76 [95% CI, 0.62 to 0.92];
conclusionOur study identified SL co-mutations in the DDR pathway as promising biomarkers for ICI efficacy. Specifically, the
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