Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types.
Discovery of cancer driver pathways is essential for targeted therapies, since these pathways govern tumor progression and treatment resistance. However, their context-specific patterns across populations remain poorly understood. Leveraging pan-cancer genomic data, we apply our two models, EntCDP a...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-08-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1013349 |
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| _version_ | 1849228233370763264 |
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| author | Wenjia Zhou Junhua Zhang |
| author_facet | Wenjia Zhou Junhua Zhang |
| author_sort | Wenjia Zhou |
| collection | DOAJ |
| description | Discovery of cancer driver pathways is essential for targeted therapies, since these pathways govern tumor progression and treatment resistance. However, their context-specific patterns across populations remain poorly understood. Leveraging pan-cancer genomic data, we apply our two models, EntCDP and ModSDP, to perform stratified analyses from four perspectives: region, tumor type, age group, and risk factors. Our results reveal the regional biases in perturbed pathways, such as PI3K-Akt in Chinese patients and GPCR in American patients with bladder cancer. Subtype comparisons highlight the mTOR signaling in lung adenocarcinoma and the FoxO signaling in lung squamous cell carcinoma. Pediatric-adult comparisons emphasize the enrichment of Ras signaling in pediatric acute myeloid leukemia and PAK signaling in pediatric glioblastoma, respectively. Risk factor associations further link Notch-mediated pathways to alcohol consumption and CDKN-regulated pathways to obesity-related cancers. Our findings demonstrate the utility of stratified driver pathway analysis in uncovering common and specific mechanisms, which can help prioritize context-aware therapeutic targets. |
| format | Article |
| id | doaj-art-849852f23d874f6d8acbe0d55fc2b1e9 |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-849852f23d874f6d8acbe0d55fc2b1e92025-08-23T05:31:15ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-08-01218e101334910.1371/journal.pcbi.1013349Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types.Wenjia ZhouJunhua ZhangDiscovery of cancer driver pathways is essential for targeted therapies, since these pathways govern tumor progression and treatment resistance. However, their context-specific patterns across populations remain poorly understood. Leveraging pan-cancer genomic data, we apply our two models, EntCDP and ModSDP, to perform stratified analyses from four perspectives: region, tumor type, age group, and risk factors. Our results reveal the regional biases in perturbed pathways, such as PI3K-Akt in Chinese patients and GPCR in American patients with bladder cancer. Subtype comparisons highlight the mTOR signaling in lung adenocarcinoma and the FoxO signaling in lung squamous cell carcinoma. Pediatric-adult comparisons emphasize the enrichment of Ras signaling in pediatric acute myeloid leukemia and PAK signaling in pediatric glioblastoma, respectively. Risk factor associations further link Notch-mediated pathways to alcohol consumption and CDKN-regulated pathways to obesity-related cancers. Our findings demonstrate the utility of stratified driver pathway analysis in uncovering common and specific mechanisms, which can help prioritize context-aware therapeutic targets.https://doi.org/10.1371/journal.pcbi.1013349 |
| spellingShingle | Wenjia Zhou Junhua Zhang Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. PLoS Computational Biology |
| title | Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. |
| title_full | Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. |
| title_fullStr | Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. |
| title_full_unstemmed | Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. |
| title_short | Multi-context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types. |
| title_sort | multi context modeling of driver pathways reveals common and specific mechanisms across 23 cancer types |
| url | https://doi.org/10.1371/journal.pcbi.1013349 |
| work_keys_str_mv | AT wenjiazhou multicontextmodelingofdriverpathwaysrevealscommonandspecificmechanismsacross23cancertypes AT junhuazhang multicontextmodelingofdriverpathwaysrevealscommonandspecificmechanismsacross23cancertypes |