Quantitative in vivo analyses reveal a complex pharmacogenomic landscape in lung adenocarcinoma Journal Article
| Authors: | Li, C.; Lin, W. Y.; Rizvi, H.; Cai, H.; McFarland, C. D.; Rogers, Z. N.; Yousefi, M.; Winters, I. P.; Rudin, C. M.; Petrov, D. A.; Winslow, M. M. |
| Article Title: | Quantitative in vivo analyses reveal a complex pharmacogenomic landscape in lung adenocarcinoma |
| Abstract: | The lack of knowledge about the relationship between tumor genotypes and therapeutic responses remains one of the most critical gaps in enabling the effective use of cancer therapies. Here, we couple a multiplexed and quantitative experimental platform with robust statistical methods to enable pharmacogenomic mapping of lung cancer treatment responses in vivo. The complex map of genotype-specific treatment responses uncovered that over 20% of possible interactions show significant resistance or sensitivity. Known and novel interactions were identified, and one of these interactions, the resistance of KEAP1-mutant lung tumors to platinum therapy, was validated using a large patient response data set. These results highlight the broad impact of tumor suppressor genotype on treatment responses and define a strategy to identify the determinants of precision therapies. © 2021 American Association for Cancer Research Inc.. All rights reserved. |
| Keywords: | cancer chemotherapy; controlled study; treatment response; gene mutation; nonhuman; animal cell; mouse; animal tissue; gene; antineoplastic metal complex; animal experiment; animal model; genotype; in vivo study; chemosensitivity; cancer resistance; cancer inhibition; lung adenocarcinoma; quantitative analysis; pharmacogenomics; keap1 gene; article |
| Journal Title: | Cancer Research |
| Volume: | 81 |
| Issue: | 17 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2021-09-01 |
| Start Page: | 4570 |
| End Page: | 4580 |
| Language: | English |
| DOI: | 10.1158/0008-5472.Can-21-0716 |
| PUBMED: | 34215621 |
| PROVIDER: | scopus |
| PMCID: | PMC8416777 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 October 2021 -- Source: Scopus |
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