Modeling lung adenocarcinoma metastases using patient-derived organoids
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 KRAS<sup>G12C</sup> 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.
Authors
- Raul Caso (ORCID: https://orcid.org/0000-0001-8414-093X)
- Gaetano Rocco (ORCID: https://orcid.org/0000-0003-4150-8604)
- Joel Rosiene (ORCID: https://orcid.org/0000-0002-8610-370X)
- Manendra B. Lankadasari
- Harry B. Lengel
- Kevin B. Johnson (ORCID: https://orcid.org/0000-0001-7990-3250)
- Marty W. Mayo (ORCID: https://orcid.org/0000-0001-9443-5926)
- James G. Connolly (ORCID: https://orcid.org/0000-0002-8742-103X)
- Matthew Joseph Bott (ORCID: https://orcid.org/0000-0003-0523-4028)
- Prasad S. Adusumilli (ORCID: https://orcid.org/0000-0002-1699-2046)
- Elizabeth G. Dunne (ORCID: https://orcid.org/0009-0003-4914-382X)
- Bob T. Li (ORCID: https://orcid.org/0000-0001-6661-8733)
- Piro Lito (ORCID: https://orcid.org/0000-0003-2196-3503)
- David R. Jones (ORCID: https://orcid.org/0000-0002-3318-0146)
- Brooke Mastrogiacomo (ORCID: https://orcid.org/0000-0003-0707-9738)
- Natasha Rekhtman (ORCID: https://orcid.org/0000-0001-5801-3144)
- Smita Sihag (ORCID: https://orcid.org/0000-0002-5041-3941)
- James M. Isbell (ORCID: https://orcid.org/0000-0002-7305-876X)
- Mark H. Bilsky (ORCID: https://orcid.org/0000-0001-6091-0709)
- Cameron Brennan (ORCID: https://orcid.org/0000-0003-4064-8891)
- Marcin Imielinski
- Yuan Liu (ORCID: https://orcid.org/0000-0002-2728-5718)
- Di He (ORCID: https://orcid.org/0000-0001-5251-823X)
- Juan Zhou (ORCID: https://orcid.org/0000-0002-5265-2364)
- Cameron N. Fick (ORCID: https://orcid.org/0000-0001-9528-0436)
- Samhita Bapat
- Huasong Tian
- Lai-Fong L Chow-Tsang
Institutions
- Memorial Sloan Kettering Cancer Center (US)
- University of Virginia (US)
- New York University (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101777
- Citations
- 17
- Primary Topic
- Cancer Cells and Metastasis
- Type
- article
- Field-Weighted Citation Impact
- 4.80
Funders
- U.S. Department of Defense
- National Institutes of Health
- National Cancer Institute