Ex-Vivo Drug-Sensitivity Testing to Predict Clinical Response in Non-Small Cell Lung Cancer and Pleural Mesothelioma: A Systematic Review and Narrative Synthesis

Our plain-English summary of Ex-Vivo Drug-Sensitivity Testing to Predict Clinical Response in Non-Small Cell Lung Cancer and Pleural Mesothelioma: A Systematic Review and Narrative Synthesis, by J. Zipprick, E. Demir, H. Krynska, et al (Cancers, 2025).

The study

• Authors: J. Zipprick, E. Demir, H. Krynska, S. Köprülüoğlu, K. Strauß, M. Skribek, R. Hutyra-Gram Ötvös, A.K.B. Gad, K. Dobra
• Journal: Cancers
• Published: 2025;17(6)
• Type of article: Review
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background/objectives: Non-small cell lung cancer and pleural mesothelioma are among the most lethal and therapy-resistant tumors in humans. These tumors are diagnosed late, frequently present pleural effusion and develop drug resistance, and the treatment is often inefficient and largely alliative. Therefore, there is an urgent need to refine the selection of drugs and patients for personalized treatment. Methods: To progress the field, we performed a systematic literature review in line with the PRISMA guidelines followed by a narrative synthesis approach to identify themes. Results: The literature to date shows, in general, a positive correlation between the drug-sensitivity of patient-derived cells ex vivo and the clinical outcome. However, only a handful of these studies show a numerical correlation. This, along with the vast diversity of correlated techniques and parameters makes it difficult to directly compare the findings. To build a common knowledge base for future studies, we therefore offer a comprehensive summary of the literature, identify gaps, and suggest future avenues for research. Conclusions: We present unified recommendations for the collection, preparation, and ex vivo sensitivity testing of samples for the future development of personalized medicine.

In plain English

This article was a systematic review, not a new study of patients. The authors searched PubMed for studies published up to the end of 2024. They looked for studies that tested anticancer drugs in the laboratory on tumor cells taken from patients with lung cancer or pleural mesothelioma, and compared those results with how the same patients responded to treatment. From almost three thousand publications they selected 19 articles. They summarized the articles in words rather than combining their numbers, because the studies did not use standardized, comparable outcomes. Only two of the 19 studies used pleural mesothelioma cells. The authors reported that 16 of the 19 articles suggested a general positive correlation between laboratory drug sensitivity and patient outcome. However, the article's counts of studies with no correlation, and of studies with numerical results, do not agree with each other. The studies that found no positive correlation used NSCLC tissue biopsies. Adding collagen or lung matrix to 3D cultures did not clearly improve prediction. The authors noted small sample sizes and inconsistent measures. They concluded that the field needs unified methods.

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: Systematic literature review following PRISMA guidelines, with a narrative synthesis (no numerical meta-analysis)
• Who was studied: Published studies found in PubMed (searched to 31 December 2024) on lung cancer and mesothelioma patients. Almost three thousand publications were screened and 19 articles were included. In the included studies, patient numbers ranged from 1 to 90.
• Exposure: Laboratory (ex vivo) testing of anticancer drugs on patient-derived tumor cells. The article does not study asbestos or any other fiber exposure.
• Main results:
  • 16 of the 19 included articles suggested a general positive correlation between ex vivo drug-sensitivity testing of patient-derived cells and patients' clinical outcome
  • The included studies that did not show a positive correlation were based on tissue biopsies of NSCLC
  • Adding collagen or lung extracellular matrix to 3D culture models did not clearly improve predictive ability compared with 3D models without added matrix
  • The authors' review indicated that 2D and 3D cancer models gave similar results
  • One included study using pleural mesothelioma cells from pleural effusions (Szulkin et al., 2014; 16 patients in the review's table) was reported as finding that patients with higher chemosensitivity had longer progression-free and overall survival. The table lists p = 0.005 for that study.
  • The only other included study listing pleural mesothelioma cells (Hillerdal et al., 2017; 8 patients with adenocarcinoma or PM, cells from pleural effusion) is listed in the table with 78% accuracy. Accuracy here means the fraction of cases where the ex vivo result matched the clinical result.
  • No numerical meta-analysis was done because the included studies lacked standardized, comparable numerical outcomes
• The authors' conclusion: The authors concluded that the field of ex vivo drug testing of patient-derived cells from lung cancer and mesothelioma needs unified principles and procedures. They highlighted what they see as advantages of high-throughput analysis of pleural-effusion-derived cells.
• Limitations the authors state:
  • The included studies had small sample sizes and did not consistently use the same parameters to establish correlations
  • The numerical correlations reported by different studies were hard to compare, because the studies used different experimental approaches and statistical methods
  • Cost-effectiveness was not assessed and was beyond the scope of the review

Topics

Medical terms in this study, explained in our Lexicon: Non-Small Cell Lung Cancer, Pleural Mesothelioma, Systematic Review, Pleural Effusion.

Related studies

• Ex Vivo Drug Sensitivity of Pleural Effusion-Derived Cells from Lung Cancer and Pleural Mesothelioma Patients Is Linked to Clinical Response — R. Hutyra-Gram Ötvös, H. Krynska, 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)
• 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)
• 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)
• Retrospective response analysis of BAP1 expression to predict the clinical activity of systemic cytotoxic chemotherapy in mesothelioma — N. Kumar, D. Alrifai, et al. (2019)

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