miR-16: expanding the range of molecular targets in mesothelioma

Our plain-English summary of miR-16: expanding the range of molecular targets in mesothelioma, by D. Fennell (The Lancet. Oncology, 2017).

The study

• Author: D. Fennell
• Journal: The Lancet. Oncology
• Published: 2017;18(10):1296-1297
• Type of article: Comment
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

In this invited comment, the author discussed a first-in-human phase 1 study by van Zandwijk and colleagues, published in the same issue of The Lancet Oncology. That study tested a miR-16 microRNA mimic delivered in bacterially derived minicells to patients with relapsed mesothelioma. The author noted that malignant mesothelioma is caused by asbestos exposure and has a devastating prognosis. Cisplatin plus pemetrexed had remained the only approved standard therapy for more than 10 years, and no somatic mutations in oncogenic kinases had been found in mesothelioma. miR-16 is a tumour suppressor microRNA that silences oncogenes such as BCL2, CCND1 and WNT3A. The same group had earlier shown that mesotheliomas often downregulate miR-16 and that restoring it was feasible in laboratory cells and in mice. The miR-16 mimic was packaged in an EGFR-targeted EnGeneIC Dream Vector, a product termed a TargomiR. In the trial, maximum glucose uptake on PET-CT fell in 9 (60%) of 15 patients assessed. Disease control was achieved in 16 (73%) of 22 patients assessed by CT, including one partial response. The author called this a respectable signal that warranted further investigation. He also noted that no post-treatment biopsies were done to confirm that the treatment acted on its target, and that no molecular stratification was applied. He suggested selecting patients by miR-16 expression and concluded that miR-16 TargomiRs could be added to a growing list of molecular targets in mesothelioma.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article is a short commentary, not an original study. The author discussed a separate phase 1 trial by van Zandwijk and colleagues, published in The Lancet Oncology. In that trial, patients with relapsed mesothelioma received a miR-16 "TargomiR". This is a synthetic copy of miR-16, a small RNA molecule that acts as a tumour suppressor, packed inside a bacterially derived shell aimed at EGFR. As the author described that trial, delivering the treatment was shown to be feasible, and tolerability was encouraging. Maximum glucose uptake on PET-CT scans fell in nine (60%) of 15 patients assessed. On CT, 16 (73%) of 22 patients assessed achieved disease control, including one patient with a partial response. The author noted that the trial took no biopsies after treatment to confirm the drug acted on miR-16's targets, and did not select patients by molecular features. The author suggested patients could be preselected by miR-16 expression. The author concluded that, compared with earlier studies in relapsed mesothelioma, the results were a respectable signal that warrants further investigation. The commentary did not study asbestos exposure.

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: Commentary (journal Comment) on a separate phase 1 trial by van Zandwijk and colleagues; the article reports no original data of its own
• Who was studied: No study population of its own; the commentary discusses a trial in patients with relapsed mesothelioma
• Exposure: Asbestos exposure was not studied. The treatment discussed was a miR-16 TargomiR: a synthetic miR-16 mimic encapsulated in an EGFR-targeted, bacterially derived shell (EnGeneIC Dream Vector)
• Main results:
  • As described by the author, the van Zandwijk trial showed that delivering the miR-16 TargomiR was feasible, with encouraging tolerability
  • In the van Zandwijk trial, treatment was associated with a drop in maximum glucose uptake on PET-CT in nine (60%) of 15 patients assessed
  • In the van Zandwijk trial, 16 (73%) of 22 patients assessed by CT achieved disease control, including one patient with a partial response
  • The author noted that the trial did no post-treatment biopsies to confirm on-target silencing of miR-16
  • The author noted that the trial applied no molecular stratification, and suggested preselecting patients by miR-16 expression
• The authors' conclusion: The author concluded that, in the context of previous studies in relapsed mesothelioma, the trial's findings were a respectable signal that warrants further investigation

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Malignant Mesothelioma, Asbestos Exposure, Prognosis, Cisplatin, Pemetrexed (Alimta), Somatic Mutation, EGFR.

Related studies

• Exosomal miR-16-5p as a target for malignant mesothelioma — P.B. Munson, E.M. Hall, et al. (2019)
• Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets — L.R. Motadi, N.L. Misso, et al. (2007)
• Molecular targets in malignant pleural mesothelioma treatment — G. Pasello, A. Favaretto (2009)
• Molecular Characterization of Malignant Mesothelioma: Time for New Targets? — C. Aggarwal, S.M. Albelda (2018)
• Molecular changes in mesothelioma with an impact on prognosis and treatment — D. Jean, J. Daubriac, et al. (2012)
• Expanding the clinical phenotype of hereditary BAP1 cancer predisposition syndrome, reporting three new cases — R. Pilarski, C.M. Cebulla, et al. (2014)

Browse more research in The Lancet. Oncology, or return to medical research.