Drug combination-wide association studies of cancer
Abstract Background Combinations of common drugs may, when taken together, have unexpected effects on incidence of diseases like cancer. It is not feasible to test for all combination drug effects in clinical trials, but in the real world, drugs are frequently taken in combination. Then, undiscovere...
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| Format: | Article |
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Nature Portfolio
2025-07-01
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| Series: | Communications Medicine |
| Online Access: | https://doi.org/10.1038/s43856-025-00991-8 |
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| author | Panagiotis Nikolaos Lalagkas Rachel Dania Melamed |
| author_facet | Panagiotis Nikolaos Lalagkas Rachel Dania Melamed |
| author_sort | Panagiotis Nikolaos Lalagkas |
| collection | DOAJ |
| description | Abstract Background Combinations of common drugs may, when taken together, have unexpected effects on incidence of diseases like cancer. It is not feasible to test for all combination drug effects in clinical trials, but in the real world, drugs are frequently taken in combination. Then, undiscovered effects may protect users of drug combinations from cancer—or increase their risk. By analyzing massive health data containing numerous people exposed to drug combinations, we have an opportunity to discover these associations. Method We describe, apply, and evaluate an approach for discovering drug combination associations with cancer using health data. Our approach builds on marginal structural model methods to emulate a randomized trial where one arm is assigned to take a drug alone, while the other arm takes that drug in combination with a second drug. Results Here, we perform drug combination-wide analysis to estimate effects of over 9000 drug combinations on incidence of all common cancer types, using claims data covering more than 100 million people. But, because the discovery of associations from observational data is always prone to confounding, we develop a number of strategies to distinguish confounding from biomedically relevant findings. We describe a robustly supported beneficial drug combination that may synergistically impact lipid levels to reduce the risk of cancer. Conclusions These findings can suggest new clinical uses for drug combinations to prevent or treat cancer. Our approach can be adapted to mine electronic health records for interactive effects on other late-onset common diseases. |
| format | Article |
| id | doaj-art-c9552a58117145bdacbfd77dc81632f5 |
| institution | Kabale University |
| issn | 2730-664X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Medicine |
| spelling | doaj-art-c9552a58117145bdacbfd77dc81632f52025-08-20T03:46:13ZengNature PortfolioCommunications Medicine2730-664X2025-07-015111210.1038/s43856-025-00991-8Drug combination-wide association studies of cancerPanagiotis Nikolaos Lalagkas0Rachel Dania Melamed1Department of Biological Sciences, University of MassachusettsDepartment of Biological Sciences, University of MassachusettsAbstract Background Combinations of common drugs may, when taken together, have unexpected effects on incidence of diseases like cancer. It is not feasible to test for all combination drug effects in clinical trials, but in the real world, drugs are frequently taken in combination. Then, undiscovered effects may protect users of drug combinations from cancer—or increase their risk. By analyzing massive health data containing numerous people exposed to drug combinations, we have an opportunity to discover these associations. Method We describe, apply, and evaluate an approach for discovering drug combination associations with cancer using health data. Our approach builds on marginal structural model methods to emulate a randomized trial where one arm is assigned to take a drug alone, while the other arm takes that drug in combination with a second drug. Results Here, we perform drug combination-wide analysis to estimate effects of over 9000 drug combinations on incidence of all common cancer types, using claims data covering more than 100 million people. But, because the discovery of associations from observational data is always prone to confounding, we develop a number of strategies to distinguish confounding from biomedically relevant findings. We describe a robustly supported beneficial drug combination that may synergistically impact lipid levels to reduce the risk of cancer. Conclusions These findings can suggest new clinical uses for drug combinations to prevent or treat cancer. Our approach can be adapted to mine electronic health records for interactive effects on other late-onset common diseases.https://doi.org/10.1038/s43856-025-00991-8 |
| spellingShingle | Panagiotis Nikolaos Lalagkas Rachel Dania Melamed Drug combination-wide association studies of cancer Communications Medicine |
| title | Drug combination-wide association studies of cancer |
| title_full | Drug combination-wide association studies of cancer |
| title_fullStr | Drug combination-wide association studies of cancer |
| title_full_unstemmed | Drug combination-wide association studies of cancer |
| title_short | Drug combination-wide association studies of cancer |
| title_sort | drug combination wide association studies of cancer |
| url | https://doi.org/10.1038/s43856-025-00991-8 |
| work_keys_str_mv | AT panagiotisnikolaoslalagkas drugcombinationwideassociationstudiesofcancer AT racheldaniamelamed drugcombinationwideassociationstudiesofcancer |