Patient-Derived Organoid Models and Precision HIPEC in Diffuse Malignant Peritoneal Mesothelioma: Modeling Heterogeneity to Address Recurrence

Our plain-English summary of Patient-Derived Organoid Models and Precision HIPEC in Diffuse Malignant Peritoneal Mesothelioma: Modeling Heterogeneity to Address Recurrence, by E.A. Makris, J.K. Ives, K. Votanopoulos (International Journal of Molecular Sciences, 2026).

The study

• Authors: E.A. Makris, J.K. Ives, K. Votanopoulos
• Journal: International Journal of Molecular Sciences
• Published: 2026;27(17)
• Type of article: Review
• Read it: PubMed · Publisher · Free full text

Abstract

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignancy for which cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is central to treatment in appropriately selected patients. Recurrence remains common even after complete macroscopic cytoreduction. Current HIPEC regimens are protocolized at the institutional and population levels but are not individualized using site-specific molecular or functional tumor biology. We performed a narrative review of clinical, genomic, epigenetic, immune, microenvironmental, and patient-derived organoid evidence relevant to DMPM, CRS/HIPEC, and treatment resistance. Recurrence is multifactorial, with plausible contributions from spatial, histologic, genomic, epigenetic, immune, stromal, and pharmacokinetic heterogeneity. Three primary reports provide direct DMPM organoid evidence, including preliminary demonstrations of patient-specific drug response and discordant responses among anatomically distinct implants. However, these platforms differ biologically, and predictive thresholds, analytical reproducibility, turnaround time, and microenvironmental modeling remain unvalidated. Multi-site organoid pharmacotyping integrated with molecular profiling is therefore a plausible strategy for studying HIPEC resistance. Translation requires a staged pathway encompassing analytical validity, blinded clinical validity, and clinical-utility testing. Precision HIPEC should presently be considered an investigational, validation-ready framework rather than a standard of care.

In plain English

This article is a narrative review, not a new study. The authors searched PubMed, Google Scholar, Scopus/Web of Science and ClinicalTrials.gov through 6 August 2026 for research on diffuse malignant peritoneal mesothelioma (DMPM). They looked at its treatment with cytoreductive surgery plus heated chemotherapy delivered into the abdomen (HIPEC), and at why the disease often comes back. They focused on patient-derived organoids: small tumor models grown from a patient's own tissue and tested with drugs in the laboratory. They identified three primary reports with direct DMPM organoid evidence. One of these included only one confirmed DMPM case. In another, by Forsythe and colleagues, heated cisplatin met that study's efficacy criterion in 12 of 16 specimens, compared with 7 of 16 for heated mitomycin C. However, pooled viability after treatment did not differ significantly between the two drugs (38.3% versus 50.6%; p = 0.10). Much of the related molecular research came from pleural rather than peritoneal mesothelioma. The authors noted that no validated threshold defines HIPEC resistance. They concluded that organoid-guided "Precision HIPEC" should remain an investigational framework, not standard care. They stated that their review was not systematic.

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: Narrative review of published literature (not a systematic review)
• Who was studied: Published clinical, genomic, epigenetic, immune, microenvironmental and organoid research relevant to diffuse malignant peritoneal mesothelioma and CRS/HIPEC, from database inception through 6 August 2026
• Exposure: The review does not study asbestos or fiber exposure. It concerns treatment: HIPEC chemotherapy regimens (such as cisplatin, doxorubicin and mitomycin C) and their testing on patient-derived organoids.
• Main results:
  • The authors identified three primary reports that provide direct organoid evidence in DMPM.
  • The earliest of these reports (Mazzocchi and colleagues) contributed only one confirmed DMPM case, in which laboratory drug sensitivity matched the patient's clinical response.
  • In a second report, Fang and colleagues grew organoids from seven DMPM tumors and one cystic peritoneal mesothelioma. Four of these lines were kept going for more than four passages. The authors of the review stated that this does not amount to blinded or prospective predictive validation.
  • In a third report, Forsythe and colleagues tested 16 evaluable specimens from seven patients. Heated cisplatin met that study's efficacy criterion in 12 of 16 specimens, compared with 7 of 16 for heated mitomycin C.
  • In the Forsythe study, pooled post-treatment viability did not differ significantly between the heated cisplatin and heated mitomycin C groups (38.3% versus 50.6%; p = 0.10).
  • Much of the molecular and single-cell research the authors reviewed came from pleural mesothelioma. The authors treated it as hypothesis-generating when applied to peritoneal disease.
  • The authors found no validated viability threshold that defines HIPEC resistance or predicts recurrence.
• The authors' conclusion: The authors concluded that organoid-informed HIPEC should remain an investigational framework rather than an established standard of care until it has been validated, including through randomized evidence.
• Limitations the authors state:
  • This was a narrative, not systematic, review. No formal risk-of-bias assessment or meta-analysis was performed.
  • The direct DMPM organoid evidence consists of three small reports that used different biological platforms.
  • Chemotherapy given before surgery while the assay is being developed may change the tumor biology being measured.

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: HIPEC, Peritoneal Mesothelioma, Cytoreductive Surgery, Molecular Profiling.

Related studies

• 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)
• FASN for diffuse malignant peritoneal mesothelioma: a prognostic biomarker after CRS+HIPEC and a therapeutic target — V. Doldi, C.M. Ciniselli, et al. (2026)
• In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening — A.R. Mazzocchi, S.A.P. Rajan, et al. (2018)
• Early recurrence after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) — G.H.C. Tan, C.S. Chia, et al. (2018)
• Dynamic evolution of NK cells and immune remodeling mediated by CRS + HIPEC: prognostic mechanisms and therapeutic implications for malignant peritoneal mesothelioma — Y.T. Liu, Q.D. Zhao, et al. (2025)
• Preventing recurrence of diffuse malignant peritoneal mesothelioma — J.C. Leinwand, J.A. Chabot, et al. (2016)

Browse more research in International Journal of Molecular Sciences, or return to medical research.