Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma

Our plain-English summary of Organoids derived from patients provide a new opportunity for research and individualized treatment of malignant peritoneal mesothelioma, by X. Fang, L. Shu, T. Chen, et al (Molecular Cancer, 2024).

The study

• Authors: X. Fang, L. Shu, T. Chen, X. Zhao, L. Yang, T. Dou, L. Yang, X. Li, M. Feng
• Journal: Molecular Cancer
• Published: 2024;23(1):12
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Malignant peritoneal mesothelioma (MPM) is an extremely rare and highly invasive tumor. Due to the lack of accurate models that reflect the biological characteristics of primary tumors, studying MPM remains challenging and is associated with an exceedingly unfavorable prognosis. This study was aimed to establish a new potential preclinical model for MPM using patient-derived MPM organoids (MPMOs) and to comprehensively evaluate the practicality of this model in medical research and its feasibility in guiding individualized patient treatment.

Methods: MPMOs were constructed using tumor tissue from MPM patients. Histopathological analysis and whole genome sequencing (WGS) were employed to determine the ability of MPMOs to replicate the original tumor's genetic and histological characteristics. The subcutaneous and orthotopic xenograft models were employed to assess the feasibility of establishing an in vivo model of MPM. MPMOs were also used to conduct drug screening and compare the results with retrospective analysis of patients after treatment, in order to evaluate the potential of MPMOs in predicting the effectiveness of drugs in MPM patients.

Results: We successfully established a culture method for human MPM organoids using tumor tissue from MPM patients and provided a comprehensive description of the necessary medium components for MPMOs. Pathological examination and WGS revealed that MPMOs accurately represented the histological characteristics and genomic heterogeneity of the original tumors. In terms of application, the success rate of creating subcutaneous and orthotopic xenograft models using MPMOs was 88% and 100% respectively. Drug sensitivity assays demonstrated that MPMOs have different medication responses, and these differences were compatible with the real situation of the patients.

Conclusion: This study presents a method for generating human MPM organoids, which can serve as a valuable research tool and contribute to the advancement of MPM research. Additionally, these organoids can be utilized as a means to evaluate the effectiveness of drug treatments for MPM patients, offering a model for personalized treatment approaches.

© 2024. The Author(s).

In plain English

This laboratory study in Wuhan, China, grew miniature three-dimensional tumor cultures, called organoids, from patients with malignant peritoneal mesothelioma. Tissue came from 8 patients who had surgery or a biopsy between January 2020 and December 2022. Seven had malignant peritoneal mesothelioma and 1 had cystic peritoneal mesothelioma. The article did not study asbestos exposure. The authors reported seven organoid lines from the seven malignant cases, calling this an 85.7% success rate. The cystic case's organoid stopped growing. In four tumor-organoid pairs checked for marker proteins and five whose DNA was sequenced, organoids matched their tumors in the markers and in most mutations. Organoids from three patients formed tumors in mice: under the skin in 8 of 9 mice (88.8%) and inside the abdomen in 9 of 9 (100%). Across 14 cancer drugs, organoids from different patients responded differently. Looking back at the patients' treatment, which included pemetrexed plus cisplatin, the authors reported outcomes consistent with the organoid results. Two malignant cases were too advanced to evaluate. They concluded the organoids are a promising model and named small sample size as the main limitation.

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: Laboratory study that grew patient-derived tumor organoids. It used tissue staining, whole genome sequencing, mouse xenograft (transplant) experiments and drug testing on the organoids, plus a retrospective comparison with the patients' own treatment outcomes.
• Who was studied: Tumor samples from 8 patients who had surgery or biopsy at Zhongnan Hospital of Wuhan University, China, from January 2020 to December 2022. Seven had malignant peritoneal mesothelioma and 1 had cystic peritoneal mesothelioma. BALB/c nude mice were used for the transplant experiments.
• Exposure: Asbestos exposure was not studied. The organoids were tested with 14 anticancer drugs used in first- or second-line treatment of malignant peritoneal mesothelioma, including pemetrexed and platinum drugs.
• Main results:
  • Seven organoid lines (more than 2 passages) were established from the seven malignant peritoneal mesothelioma patients. The authors reported this as an 85.7% success rate.
  • The organoid grown from the cystic peritoneal mesothelioma patient declined and died after its first passage.
  • In four tumor-organoid pairs, the diagnostic markers CK5/6, WT-1 and calretinin in each organoid matched the original tumor.
  • In whole genome sequencing of five tumor-organoid pairs, most somatic mutations in each tumor were kept in its organoid.
  • Mutations in the genes VPS13D and MAP3K6 were found in 4 of the 5 sequenced tumor-organoid pairs.
  • Organoids from three patients (C2, C6, C7) were each transplanted into three nude mice per model. Tumors formed under the skin in 88.8% of mice, which is 8 of 9 (C2 2/3, C6 3/3, C7 3/3). They formed inside the abdomen in 100%, which is 9 of 9 (3/3 for each line).
  • Most ordinary two-dimensional cell cultures from the patients stopped growing and died after the third generation. Only the Case 6 cell line lasted more than 10 generations.
  • Organoids from patients C1, C5 and C7 were poorly inhibited by pemetrexed and platinum drugs. Organoids from patients C3, C4 and C6 were significantly inhibited.
  • In the retrospective look at patients' treatment, the patients received the pemetrexed plus cisplatin regimen, and its efficacy differed between patients.
  • Patients C1 and C7 kept having tumor growth during treatment and survived about 6 months.
  • Patients C3 and C4 responded to the treatment regimen and survived more than 20 months.
  • For the patients who could be evaluated, the authors reported that actual treatment response was consistent with their organoids' drug sensitivity results. Patients C5 and C6 could not be evaluated.
• The authors' conclusion: The authors concluded that organoids from malignant peritoneal mesothelioma patients are a promising new preclinical model that represents individual patients. They said such organoids could be used for research and for testing which drugs may work for a given patient.
• Limitations the authors state:
  • The small sample size was the most significant limitation, and more clinical validation cases are needed.
  • During long-term culture, the varied tumor cells may change or disappear, which can affect precision. The authors therefore suggested using early organoids for drug testing.
  • All the malignant cases were of a single subtype (described as epithelial type), so other subtypes were not tested.
  • Patients C5 and C6 could not be assessed for treatment response because they were at a terminal stage when diagnosed.
  • There were too few cystic peritoneal mesothelioma samples to study further why that organoid failed.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma, Peritoneal mesothelioma.

Medical terms in this study, explained in our Lexicon: Peritoneal Mesothelioma, Prognosis.

Related studies

• Patient-Derived Organoid Models and Precision HIPEC in Diffuse Malignant Peritoneal Mesothelioma: Modeling Heterogeneity to Address Recurrence — E.A. Makris, J.K. Ives, et al. (2026)
• Cisplatin exhibits superiority over MMC as a perfusion agent in a peritoneal mesothelioma patient specific organoid HIPEC platform — S.D. Forsythe, R.A. Erali, et al. (2023)
• In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening — A.R. Mazzocchi, S.A.P. Rajan, et al. (2018)
• Conditional survival patterns and individualized prognostic prediction in malignant peritoneal mesothelioma — X. Liao, C. Li, et al. (2026)
• Multipotent cancer stem cells derived from human malignant peritoneal mesothelioma promote tumorigenesis — S. Varghese, R. Whipple, et al. (2012)
• Fluorescence in situ hybridization (FISH) provides estimates of minute and interstitial BAP1, CDKN2A, and NF2 gene deletions in peritoneal mesothelioma — S. Brich, F. Bozzi, et al. (2020)

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