Editorial: Novel agents and combinations for treatment of malignant pleural mesothelioma in pre-clinical models

Our plain-English summary of Editorial: Novel agents and combinations for treatment of malignant pleural mesothelioma in pre-clinical models, by S.K. Lam, S.E. Mutsaers (Frontiers in Pharmacology, 2022).

The study

• Authors: S.K. Lam, S.E. Mutsaers
• Journal: Frontiers in Pharmacology
• Published: 2022;13:1015959
• Type of article: Editorial
• Read it: PubMed · Publisher · Free full text

In plain English

This article was an editorial, not a research study, and reported no new data. The authors introduced a collection of articles in Frontiers in Pharmacology about testing new drugs and drug combinations for malignant pleural mesothelioma in laboratory cell and animal models. They described this cancer as strongly associated with asbestos exposure. The editorial summarized four of the collected articles. Robinson et al. reviewed their mouse models, including an asbestos-induced mouse model said to produce mesothelioma in 100% of animals given asbestos. Pezzicoli et al. reviewed current treatments and new drugs in clinical trials, including lurbinectedin. Lapidot et al. reviewed three possible drug targets (STAT3, KDM4A and heparanase) that have not yet entered clinical trials. Oien et al. reported that the antimalarial drug quinacrine had anti-cancer effects in mesothelioma cell lines resistant to cisplatin and pemetrexed, though its effect in living animals had not been studied. The authors wrote that many laboratory studies fail to achieve their full potential in human trials. They gave funding, poor trial design and a possible disconnect between basic scientists and clinical researchers as reasons, and they called for closer collaboration.

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: editorial introducing a collection of articles (Research Topic); no original data
• Main results:
  • The editorial described a review by Robinson et al. of the authors' own use of mouse models. These included the MexTAg mouse, an asbestos-induced model said to generate 100% mesotheliomas in response to asbestos.
  • The editorial described a review by Pezzicoli et al. that discussed novel agents in clinical trials. It reported that mesothelioma cell lines were highly sensitive to lurbinectedin and that the drug showed activity in the SAKK 17/16 phase II trial.
  • The editorial cited the MiST2 phase II trial of abemaciclib in MPM patients deficient in p16ink4A (Fennell et al., 2022). In that trial, median progression free survival was 128 days and median overall survival was 217 days.
  • The editorial described a review by Lapidot et al. of three emerging targets in MPM (STAT3, KDM4A and heparanase) that have not yet entered clinical trial.
  • The editorial described a study by Oien et al. in which quinacrine had anti-cancer effects in cisplatin-resistant and pemetrexed-resistant MPM cell lines. NF2-mutated cell lines were more sensitive to the drug.
  • The effect of quinacrine in vivo had not been investigated.
  • The authors stated that many preclinical studies fail to achieve their full potential in human trials. They gave reasons such as funding and poor trial design, and said a disconnect between basic scientists and clinical researchers may also be a cause.
• The authors' conclusion: The authors suggested that scientists and clinicians collaborate to plan better animal studies and clinical trials for diseases like MPM.

Topics

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

Related studies

• Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma — J. Green, Y. Dundar, et al. (2007)
• Chemosensitivity of three patient-derived primary cultures of canine pericardial mesothelioma by single-agent and combination treatment — R. Nabeta, A. Kanaya, et al. (2023)
• Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma — N. Sobhani, S.P. Corona, et al. (2017)
• Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements — D.C. Christoph, W.E. Eberhardt (2014)
• A Novel Clinical Prediction Model for Prognosis in Malignant Pleural Mesothelioma Using Decision Tree Analysis — F.J. Brims, T.M. Meniawy, et al. (2016)
• A novel BH3-mimetic, AZD0466, targeting BCL-XL and BCL-2 is effective in pre-clinical models of malignant pleural mesothelioma — S. Arulananda, M. O'Brien, et al. (2021)

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