Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?

Our plain-English summary of Organoids as a Model for Precision Medicine in Malignant Pleural Mesothelioma: Where Are We Today?, by Y. Gao, M. Kruithof-de Julio, R.W. Peng, et al (Cancers, 2022).

The study

• Authors: Y. Gao, M. Kruithof-de Julio, R.W. Peng, P. Dorn
• Journal: Cancers
• Published: 2022;14(15)
• Type of article: Review
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

MPM is an aggressive tumor originating from pleural mesothelial cells. A characteristic feature of the disease is the dominant prevalence of therapeutically intractable inactivating alterations in TSGs, making MPM one of the most difficult cancers to treat and the epitome of a cancer characterized by a significant lack of therapy options and an extremely poor prognosis (5-year survival rate of only 5% to 10%). Extensive interpatient heterogeneity poses another major challenge for targeted therapy of MPM, warranting stratified therapy for specific subgroups of MPM patients. Accurate preclinical models are critical for the discovery of new therapies and the development of personalized medicine. Organoids, an in vitro 'organ-like' 3D structure derived from patient tumor tissue that faithfully mimics the biology and complex architecture of cancer and largely overcomes the limitations of other existing models, are the next-generation tumor model. Although organoids have been successfully produced and used in many cancers, the development of MPM organoids is still in its infancy. Here, we provide an overview of recent advances in cancer organoids, focusing on the progress and challenges in MPM organoid development. We also elaborate the potential of MPM organoids for understanding MPM pathobiology, discovering new therapeutic targets, and developing personalized treatments for MPM patients.

In plain English

This article is a review; the authors reported no data of their own. It surveyed published research on patient-derived organoids (three-dimensional cultures grown in the laboratory from a patient's tumor tissue) and their possible use for malignant pleural mesothelioma (MPM). The authors stated that earlier three-dimensional mesothelioma models, mainly spheroids, did not significantly overcome the shortcomings of flat (2D) cell cultures. The one mesothelioma organoid study they described, from 2018, grew organoids from two patients with epithelioid peritoneal mesothelioma, not pleural mesothelioma, on a microfluidic chip and reported them suitable for drug screening. The authors stated that drug screening with MPM organoids had not yet been reported, and that how to set culture conditions remained unclear. They suggested that organoids from normal pleura might be used to study how asbestos causes disease, presenting this as a possibility. The authors concluded that organoids hold promise for personalized MPM treatment, and that culture and drug-screening methods need standardizing.

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; no new data
• Who was studied: No patients were studied. The review covered published work on cancer organoids in general and on three-dimensional laboratory models of mesothelioma, including one organoid study using tumor tissue from two patients with epithelioid peritoneal mesothelioma.
• Exposure: No exposure was studied. Asbestos was mentioned only as background: the authors called it the major risk factor for MPM and said the mechanism by which it causes cancer is not fully understood.
• Main results:
  • The authors stated that earlier three-dimensional mesothelioma models, mainly spheroids from tumor tissue or cell lines, did not significantly overcome the shortcomings of 2D culture.
  • A 2018 study cited by the authors (reference 82) generated organoids from two patients with epithelioid peritoneal mesothelioma using a microfluidic tumor-on-a-chip. The study reported that these organoids retained the mesothelioma phenotype and were suitable for drug screening. The authors noted that the method requires special equipment.
  • The authors stated that drug screening with MPM organoids had not yet been reported.
  • The authors listed three unresolved challenges for MPM organoids: unclear culture conditions, MPM cell secretions that may destroy the Matrigel gel before organoids mature, and incomplete reproduction of the tumor microenvironment.
  • The authors stated that mouse models of asbestos-induced MPM differ genetically from human MPM. They suggested that organoids derived from normal pleura may be an option for studying the role of asbestos in causing disease.
• The authors' conclusion: The authors concluded that ongoing efforts to model MPM with patient-derived organoids hold promise for finding new personalized treatments. They added that standardizing organoid culture and drug screening is a prerequisite.
• Limitations the authors state:
  • Limitation of organoid models, as stated by the authors: culturing organoids takes more time and resources than other cancer models.
  • Limitation of organoid models, as stated by the authors: organoids lack blood vessels.
  • Limitation of organoid models, as stated by the authors: it remains hard to include all cell types of the tumor microenvironment.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Prognosis, Targeted Therapy, Discovery.

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