Modeling lung adenocarcinoma metastases using patient-derived organoids

被引：11

作者：

Liu, Yuan ^{[1
,2
]}

Lankadasari, Manendra ^{[1
,2
]}

Rosiene, Joel ^{[3
]}

Johnson, Kofi E. ^{[4
,5
]}

Zhou, Juan ^{[1
,2
]}

Bapat, Samhita ^{[1
,2
]}

Chow-Tsang, Lai-Fong L. ^{[1
,2
]}

Tian, Huasong ^{[3
]}

Mastrogiacomo, Brooke ^{[1
,2
,6
]}

He, Di ^{[1
,2
]}

Connolly, James G. ^{[1
,2
]}

Lengel, Harry B. ^{[1
,2
]}

Caso, Raul ^{[1
,2
]}

Dunne, Elizabeth G. ^{[1
,2
]}

Fick, Cameron N. ^{[1
,2
]}

Rocco, Gaetano ^{[1
,2
]}

Sihag, Smita ^{[1
]}

Isbell, James M. ^{[1
,2
]}

Bott, Mathew J. ^{[1
,2
]}

Li, Bob T. ^{[7
]}

Lito, Piro

Brennan, Cameron W. ^{[8
]}

Bilsky, Mark H. ^{[8
]}

Rekhtman, Natasha ^{[2
,9
]}

Adusumilli, Prasad S. ^{[1
,2
]}

Mayo, Marty W. ^{[10
]}

Imielinski, Marcin

Jones, David R. ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Surg, Thorac Serv, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Fiona & Stanley Druckenmiller Ctr Lung Canc Res, New York, NY 10065 USA

[3] NYU, Dept Pathol, New York, NY USA

[4] Weill Cornell Med, Meyer Canc Ctr, New York, NY USA

[5] Triinst PhD Program Computat Biol & Med, New York, NY USA

[6] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Computat Oncol Serv, New York, NY USA

[7] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY USA

[8] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY USA

[9] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA

[10] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA

来源：

CELL REPORTS MEDICINE | 2024年 / 5卷 / 10期

基金：

美国国家卫生研究院;

关键词：

CANCER; RECURRENCE; ACTIVATION; MUTATIONS; STRATEGY; TUMORS; GENE;

D O I：

10.1016/j.xcrm.2024.101777

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 wholegenome 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 G12C 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.

引用

页数：18

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