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- Title
Clinical application of a lung cancer organoid (tumoroid) culture system.
- Authors
Yokota, Etsuko; Iwai, Miki; Yukawa, Takuro; Yoshida, Masakazu; Naomoto, Yoshio; Haisa, Minoru; Monobe, Yasumasa; Takigawa, Nagio; Guo, Minzhe; Maeda, Yutaka; Fukazawa, Takuya; Yamatsuji, Tomoki
- Abstract
Despite high expectations for lung tumoroids, they have not been applied in the clinic due to the difficulty of their long-term culture. Here, however, using AO (airway organoid) media developed by the Clevers laboratory, we succeeded in generating 3 lung tumoroid lines for long-term culture (>13 months) from 41 lung cancer cases (primary or metastatic). Use of nutlin-3a was key to selecting lung tumoroids that harbor mutant p53 in order to eliminate normal lung epithelial organoids. Next-generation sequencing (NGS) analysis indicated that each lung tumoroid carried BRAFG469A, TPM3-ROS1 or EGFRL858R/RB1E737*, respectively. Targeted therapies using small molecule drugs (trametinib/erlotinib for BRAFG469A, crizotinib/entrectinib for TPM3-ROS1 and ABT-263/YM-155 for EGFRL858R/RB1E737*) significantly suppressed the growth of each lung tumoroid line. AO media was superior to 3 different media developed by other laboratories. Our experience indicates that long-term lung tumoroid culture is feasible, allowing us to identify NGS-based therapeutic targets and determine the responsiveness to corresponding small molecule drugs.
- Subjects
ORGANOIDS; NUCLEOTIDE sequencing; LUNG tumors; CELL culture; BIOMEDICAL engineering
- Publication
NPJ Precision Oncology, 2021, Vol 5, Issue 1, p1
- ISSN
2397-768X
- Publication type
Article
- DOI
10.1038/s41698-021-00166-3