Modeling lung adenocarcinoma metastases using patient-derived organoids Journal Article
| Authors: | Liu, Y.; Lankadasari, M.; Rosiene, J.; Johnson, K. E.; Zhou, J.; Bapat, S.; Chow-Tsang, L. F. L.; Tian, H.; Mastrogiacomo, B.; He, D.; Connolly, J. G.; Lengel, H. B.; Caso, R.; Dunne, E. G.; Fick, C. N.; Rocco, G.; Sihag, S.; Isbell, J. M.; Bott, M. J.; Li, B. T.; Lito, P.; Brennan, C. W.; Bilsky, M. H.; Rekhtman, N.; Adusumilli, P. S.; Mayo, M. W.; Imielinski, M.; Jones, D. R. |
| Article Title: | Modeling lung adenocarcinoma metastases using patient-derived organoids |
| Abstract: | Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRASG12C PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD. © 2024 The Author(s) |
| Keywords: | genetics; mouse; animal; metabolism; animals; mice; metastasis; biological model; models, biological; lung neoplasms; pathology; lung tumor; lung adenocarcinoma; mononuclear cell; leukocytes, mononuclear; neoplasm metastasis; protein p21; proto-oncogene proteins p21(ras); adenocarcinoma of lung; humans; human; organoids; organoid |
| Journal Title: | Cell Reports Medicine |
| Volume: | 5 |
| Issue: | 10 |
| ISSN: | 2666-3791 |
| Publisher: | Cell Press |
| Date Published: | 2024-10-15 |
| Start Page: | 101777 |
| Language: | English |
| DOI: | 10.1016/j.xcrm.2024.101777 |
| PUBMED: | 39413736 |
| PROVIDER: | scopus |
| PMCID: | PMC11513837 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PDF -- MSK corresponding author is David Jones -- Source: Scopus |
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