Spheroids Generated from Malignant Pleural Effusion as a Tool to Predict the Response of Non-Small Cell Lung Cancer to Treatment

Author:

Yang Tsung-Ming12ORCID,Fang Yu-Hung13,Lin Chieh-Mo1,Chen Miao-Fen4,Lin Chun-Liang567ORCID

Affiliation:

1. Division of Pulmonary and Critical Care Medicine, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan

2. School of Traditional Chinese Medicine, Chang Gung University, Taoyuan 333423, Taiwan

3. Department of Respiratory Care, Chang Gung University of Science and Technology, Chiayi 613016, Taiwan

4. Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan

5. Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 613016, Taiwan

6. Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 613016, Taiwan

7. College of Medicine, Chang Gung University, Taoyuan 333423, Taiwan

Abstract

Background: Spheroids generated by tumor cells collected from malignant pleural effusion (MPE) were shown to retain the characteristics of the original tumors. This ex vivo model might be used to predict the response of non-small cell lung cancer (NSCLC) to anticancer treatments. Methods: The characteristics, epidermal growth factor receptor (EGFR) mutation status, and clinical response to EGFR-TKIs treatment of enrolled patients were recorded. The viability of the spheroids generated from MPE of enrolled patients were evaluated by visualization of the formazan product of the MTT assay. Results: Spheroids were generated from 14 patients with NSCLC-related MPE. Patients with EGFR L861Q, L858R, or Exon 19 deletion all received EGFR-TKIs, and five of these seven patients responded to treatment. The viability of the spheroids generated from MPE of these five patients who responded to EGFR-TKIs treatment was significantly reduced after gefitinib treatment. On the other hand, gefitinib treatment did not reduce the viability of the spheroids generated from MPE of patients with EGFR wild type, Exon 20 insertion, or patients with sensitive EGFR mutation but did not respond to EGFR-TKIs treatment. Conclusion: Multicellular spheroids generated from NSCLC-related MPE might be used to predict the response of NSCLC to treatment.

Funder

Chang Gung Memorial Hospital

Publisher

MDPI AG

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