Genome-level selection in tumors as a universal marker of resistance to therapy
Abstract Tumor evolution is shaped by selective pressures imposed by physiological factors as the tumor naturally progresses to colonize local and distant tissues, as well as by therapy. However, the distinction between these two types of pressures and their impact on tumor evolution remain elusive,...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61709-x |
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| author | Erez Persi Praneeth R. Sudalagunta Yuri I. Wolf Rafael R. Canevarolo Mehdi Damaghi Kenneth H. Shain Ariosto S. Silva Eugene V. Koonin |
| author_facet | Erez Persi Praneeth R. Sudalagunta Yuri I. Wolf Rafael R. Canevarolo Mehdi Damaghi Kenneth H. Shain Ariosto S. Silva Eugene V. Koonin |
| author_sort | Erez Persi |
| collection | DOAJ |
| description | Abstract Tumor evolution is shaped by selective pressures imposed by physiological factors as the tumor naturally progresses to colonize local and distant tissues, as well as by therapy. However, the distinction between these two types of pressures and their impact on tumor evolution remain elusive, mainly, due to extensive intra-tumor heterogeneity. To disentangle the effects of these selective pressures, we analyze data from diverse cohorts of patients, of both treated and untreated cancers. We find that, despite the wide variation across patients, the selection strength on tumor genomes in individual patients is stable and largely unaffected by tumor progression in the primary settings, with some cancer-specific signatures detectable in the progression to metastases. However, we identify a nearly universal shift toward neutral evolution in tumors that resist treatment and demonstrate that this regime is associated with worse prognosis. We validate these findings on both published and original datasets. We suggest that monitoring the selection regime during cancer treatment can assist clinical decision-making in many cases. |
| format | Article |
| id | doaj-art-8ed8ac8f67874300a0c858f476ad75c5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-8ed8ac8f67874300a0c858f476ad75c52025-08-20T03:43:11ZengNature PortfolioNature Communications2041-17232025-07-0116111510.1038/s41467-025-61709-xGenome-level selection in tumors as a universal marker of resistance to therapyErez Persi0Praneeth R. Sudalagunta1Yuri I. Wolf2Rafael R. Canevarolo3Mehdi Damaghi4Kenneth H. Shain5Ariosto S. Silva6Eugene V. Koonin7Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of HealthDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research InstituteComputational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of HealthDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Pathology, School of Medicine, Stony Brook UniversityDepartments of Malignant Hematology and Molecular Medicine, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center and Research InstituteComputational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of HealthAbstract Tumor evolution is shaped by selective pressures imposed by physiological factors as the tumor naturally progresses to colonize local and distant tissues, as well as by therapy. However, the distinction between these two types of pressures and their impact on tumor evolution remain elusive, mainly, due to extensive intra-tumor heterogeneity. To disentangle the effects of these selective pressures, we analyze data from diverse cohorts of patients, of both treated and untreated cancers. We find that, despite the wide variation across patients, the selection strength on tumor genomes in individual patients is stable and largely unaffected by tumor progression in the primary settings, with some cancer-specific signatures detectable in the progression to metastases. However, we identify a nearly universal shift toward neutral evolution in tumors that resist treatment and demonstrate that this regime is associated with worse prognosis. We validate these findings on both published and original datasets. We suggest that monitoring the selection regime during cancer treatment can assist clinical decision-making in many cases.https://doi.org/10.1038/s41467-025-61709-x |
| spellingShingle | Erez Persi Praneeth R. Sudalagunta Yuri I. Wolf Rafael R. Canevarolo Mehdi Damaghi Kenneth H. Shain Ariosto S. Silva Eugene V. Koonin Genome-level selection in tumors as a universal marker of resistance to therapy Nature Communications |
| title | Genome-level selection in tumors as a universal marker of resistance to therapy |
| title_full | Genome-level selection in tumors as a universal marker of resistance to therapy |
| title_fullStr | Genome-level selection in tumors as a universal marker of resistance to therapy |
| title_full_unstemmed | Genome-level selection in tumors as a universal marker of resistance to therapy |
| title_short | Genome-level selection in tumors as a universal marker of resistance to therapy |
| title_sort | genome level selection in tumors as a universal marker of resistance to therapy |
| url | https://doi.org/10.1038/s41467-025-61709-x |
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