Understanding metastasis mixed-treatment responses through genomic analyses
Abstract Early-stage and metastatic breast cancers (MBC) can exhibit genomic heterogeneity, even within the same individual. Response to therapy in metastatic breast cancer patients with multiple metastases can also be heterogeneous, with different degrees of responsiveness to the same drug(s) acros...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Breast Cancer |
| Online Access: | https://doi.org/10.1038/s41523-025-00724-z |
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| author | Susana Garcia-Recio Paola Zagami Brooke M. Felsheim Amy Wheless Kerry Thomas Renato Trimarchi Lisa A. Carey Charles M. Perou |
| author_facet | Susana Garcia-Recio Paola Zagami Brooke M. Felsheim Amy Wheless Kerry Thomas Renato Trimarchi Lisa A. Carey Charles M. Perou |
| author_sort | Susana Garcia-Recio |
| collection | DOAJ |
| description | Abstract Early-stage and metastatic breast cancers (MBC) can exhibit genomic heterogeneity, even within the same individual. Response to therapy in metastatic breast cancer patients with multiple metastases can also be heterogeneous, with different degrees of responsiveness to the same drug(s) across metastatic sites, termed “mixed response,” within the same patient. Whether this treatment response variability is influenced by factors such as intrinsic tumor characteristics of metastatic lesions and/or the microenvironment is unknown. Through genomic analysis of multiple metastases from the same patient, assayed in 6 different patients who had exhibited mixed response on imaging, we identified that higher regulatory T cells (T reg) and CDKN2A gene expression values correlate with non-response, while the KRAS gene, KRAS amplicon, and CD8T cells were associated with response in individual metastases. These genomic features may explain mixed clinical responses and provide valuable insights into intrapatient variations in treatment sensitivity. |
| format | Article |
| id | doaj-art-265bcaabe0d64343b2e21532c9765adb |
| institution | Kabale University |
| issn | 2374-4677 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Breast Cancer |
| spelling | doaj-art-265bcaabe0d64343b2e21532c9765adb2025-02-02T12:35:30ZengNature Portfolionpj Breast Cancer2374-46772025-01-011111810.1038/s41523-025-00724-zUnderstanding metastasis mixed-treatment responses through genomic analysesSusana Garcia-Recio0Paola Zagami1Brooke M. Felsheim2Amy Wheless3Kerry Thomas4Renato Trimarchi5Lisa A. Carey6Charles M. Perou7Department of Genetics, University of North Carolina at Chapel HillDivision of Medical Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel HillBioinformatics and Computational Biology Curriculum, University of North Carolina at Chapel HillDivision of Medical Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel HillDepartment of Radiology, School of Medicine, University of North Carolina at Chapel HillDiagnostic and Interventional Radiology Unit, BIOMORF Department, University of MessinaDivision of Medical Oncology, Department of Medicine, School of Medicine, University of North Carolina at Chapel HillDepartment of Genetics, University of North Carolina at Chapel HillAbstract Early-stage and metastatic breast cancers (MBC) can exhibit genomic heterogeneity, even within the same individual. Response to therapy in metastatic breast cancer patients with multiple metastases can also be heterogeneous, with different degrees of responsiveness to the same drug(s) across metastatic sites, termed “mixed response,” within the same patient. Whether this treatment response variability is influenced by factors such as intrinsic tumor characteristics of metastatic lesions and/or the microenvironment is unknown. Through genomic analysis of multiple metastases from the same patient, assayed in 6 different patients who had exhibited mixed response on imaging, we identified that higher regulatory T cells (T reg) and CDKN2A gene expression values correlate with non-response, while the KRAS gene, KRAS amplicon, and CD8T cells were associated with response in individual metastases. These genomic features may explain mixed clinical responses and provide valuable insights into intrapatient variations in treatment sensitivity.https://doi.org/10.1038/s41523-025-00724-z |
| spellingShingle | Susana Garcia-Recio Paola Zagami Brooke M. Felsheim Amy Wheless Kerry Thomas Renato Trimarchi Lisa A. Carey Charles M. Perou Understanding metastasis mixed-treatment responses through genomic analyses npj Breast Cancer |
| title | Understanding metastasis mixed-treatment responses through genomic analyses |
| title_full | Understanding metastasis mixed-treatment responses through genomic analyses |
| title_fullStr | Understanding metastasis mixed-treatment responses through genomic analyses |
| title_full_unstemmed | Understanding metastasis mixed-treatment responses through genomic analyses |
| title_short | Understanding metastasis mixed-treatment responses through genomic analyses |
| title_sort | understanding metastasis mixed treatment responses through genomic analyses |
| url | https://doi.org/10.1038/s41523-025-00724-z |
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