Ex Vivo Drug Sensitivity of Pleural Effusion-Derived Cells from Lung Cancer and Pleural Mesothelioma Patients Is Linked to Clinical Response

Our plain-English summary of Ex Vivo Drug Sensitivity of Pleural Effusion-Derived Cells from Lung Cancer and Pleural Mesothelioma Patients Is Linked to Clinical Response, by R. Hutyra-Gram Ötvös, H. Krynska, G. Gudoityte, et al (Cancers, 2025).

The study

• Authors: R. Hutyra-Gram Ötvös, H. Krynska, G. Gudoityte, M. Skribek, A. Oniscu, O. Berkovska, K. Strauß, J. Zipprick, D. Tamborero, A. Alexeyenko, A.K.B. Gad, B. Seashore-Ludlow, K. Dobra
• Journal: Cancers
• Published: 2025;17(14)
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Tumors of the pleura, such as metastatic lung cancer and mesothelioma, are amongst the most lethal and therapy-resistant tumors. The first manifestation of the disease is often pleural effusion, the first available material for diagnosis. The five-year survival rate is exceptionally low, around 10-20%, and only a small proportion of patients harbor mutations that allow targeted treatments. Almost all patients develop resistance to treatment, which is often palliative. There is therefore an urgent need to refine the selection of drugs and patients for personalized treatment.

Methods: We isolated and cultured cells from pleural effusions in 3D cell aggregates and compared their drug sensitivity ex vivo to the clinical response to the same chemotherapeutic agents, combined with targeted sequencing and network analysis.

Results: The ex vivo drug response showed a positive correlation with the treatment response and survival of patients in the clinic, with a stronger link to overall survival than to progression-free survival. Cryopreserved cells showed a similar response to freshly collected cells from the clinic.

Conclusions: The findings advance the field of ex vivo screening and present an opportunity to combine strategies for functional precision medicine with comprehensive characterization of disease for improved treatment and future management of lung cancer.

In plain English

This retrospective double-blind observational cohort study at Karolinska University Hospital, Sweden, compared laboratory drug responses of cancer cells from pleural effusions (fluid around the lungs) with patients' outcomes. Of 543 patients with malignant effusion, 21 were included (19 adenocarcinoma, 2 mesothelioma). Cells were grown as 3D clusters and tested against 14 approved drugs and 3 drug pairs. Of 27 samples, 10 failed the laboratory quality check. Of 5 fresh–frozen pairs, 2 passed quality checks in both forms; these showed no statistically significant difference in drug response. Nine patients entered the comparison; for three-drug regimens, the authors used the laboratory score for carboplatin with pemetrexed only. In them, laboratory sensitivity showed moderate positive correlations, neither statistically significant, with survival after the effusion (r = 0.32, p = 0.39) and progression-free survival (r = 0.37, p = 0.31). Median survival was 94 days with low and 1009 days with high sensitivity, a difference that was not statistically significant. The authors described this as a trend. They noted that the small, varied group, a high risk of selection bias and the assay's lack of immune-cell components limit the findings.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective double-blind observational cohort study combining laboratory (ex vivo) drug testing of patient cells with clinical follow-up, targeted sequencing and network analysis
• Who was studied: 21 patients with malignant pleural effusion, selected from 543 patients diagnosed with malignant effusion at Karolinska University Hospital, Sweden. They were diagnosed between 1 April 2021 and 17 November 2021 and between 18 January 2023 and 13 January 2025. 19 had adenocarcinoma (metastatic non-small-cell lung cancer) and 2 had pleural mesothelioma. Only 9 patients were included in the correlation analysis.
• Exposure: Laboratory exposure of pleural effusion cells to 14 FDA-approved cancer drugs at 5 concentrations from 1 nM to 10,000 nM, plus 3 two-drug combinations (carboplatin with pemetrexed, gemcitabine or vinorelbine). The article does not study asbestos or any other environmental or occupational exposure.
• Main results:
  • Of 27 samples from 21 patients, 10 failed the assay quality control and were excluded.
  • Of 5 fresh–frozen sample pairs, 2 passed quality control in both forms and 3 failed.
  • There was no statistically significant difference in drug sensitivity between fresh and frozen samples, either for single drugs (p = 0.909) or for combinations (p = 0.145).
  • Of the 21 patients, 9 were included in the correlation analysis.
  • For patients who had received triple therapy, the correlation used the laboratory score for carboplatin with pemetrexed (at 10 µM carboplatin), not for the full regimen.
  • In the 9 patients, the drug sensitivity score showed a moderate positive correlation with overall survival after the pleural effusion (r = 0.32, p = 0.39).
  • In the 9 patients, the correlation between the drug sensitivity score and progression-free survival was moderate and not statistically significant (r = 0.37, p = 0.31).
  • When the 9 patients were split at the median drug sensitivity score, median overall survival was 94 days in the low-score group and 1009 days in the high-score group.
  • The survival difference between the two groups was not statistically significant (Mantel–Cox p = 0.127; Gehan–Breslow–Wilcoxon p = 0.093).
  • The hazard ratio for the low-score versus the high-score group was 3.998 (95% CI 0.6751 to 23.68).
• The authors' conclusion: The authors concluded that the analyses suggest a trend toward worse survival in patients whose cells were less sensitive in the laboratory, and noted that the small sample limits statistical power. They described laboratory drug screening of pleural-effusion cells as a promising opportunity to identify treatment options.
• Limitations the authors state:
  • The low inclusion rate creates a high risk of selection bias and limits statistical power.
  • The results are mainly descriptive because of the cohort's heterogeneity and size.
  • Follow-up time varied widely between patients.
  • The assay lacks immune-cell components, which limits assessment of drug effects that work through the immune system. The authors also did not evaluate the immune cell population in the patients' effusions.
  • None of the samples from patients who received osimertinib showed sensitivity in the screen, possibly because the culture medium contained EGF.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Effusion, Lung Cancer, Pleural Mesothelioma, Pleura, Mesothelioma, Palliative Care, Overall Survival, Progression-Free Survival.

Related studies

• Ex-Vivo Drug-Sensitivity Testing to Predict Clinical Response in Non-Small Cell Lung Cancer and Pleural Mesothelioma: A Systematic Review and Narrative Synthesis — J. Zipprick, E. Demir, et al. (2025)
• Characterization and drug sensitivity profiling of primary malignant mesothelioma cells from pleural effusions — A. Szulkin, R. Otvös, et al. (2014)
• Variation in drug sensitivity of malignant mesothelioma cell lines with substantial effects of selenite and bortezomib, highlights need for individualized therapy — A. Szulkin, G. Nilsonne, et al. (2013)
• Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines — A.M. Hand, K. Husgafvel-Pursiainen, et al. (1992)
• STRN-ALK rearranged pediatric malignant peritoneal mesothelioma - Functional testing of 527 cancer drugs in patient-derived cancer cells — A. Murumägi, D. Ungureanu, et al. (2021)
• In vitro and in vivo characterization of highly purified human mesothelioma derived cells — A. Melotti, A. Daga, et al. (2010)

Browse more research in Cancers, or return to medical research.