Artichoke phytocomplex modulates serum microRNAs in patients exposed to asbestos: a first step of a phase II clinical trial.

Paola Muti, Andrea Sacconi, Claudio Pulito, Giulia Orlandi, Sara Donzelli, Aldo Morrone, James Jiulian, Gerard P Cox, Martin Kolb, Gregory Pond, Peter Kavsak, Mark Norman Levine, Giovanni Blandino, Sabrina Strano

Journal: Journal of experimental & clinical cancer research : CR 2022;41(1):255

PMID: 35987988

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Abstract

BACKGROUND

Malignant pleural mesothelioma is a highly aggressive tumor associated with asbestos exposure. There are few effective treatment options for mesothelioma, and patients have a very poor prognosis. Mesothelioma has the potential to represent an appropriate disease to prevent because of its strong association with asbestos exposure and the long latency from exposure to the disease on-set.

METHODS

In the present study, we tested biological activity and toxicity of an artichoke freeze-dried extract (AWPC) as potential complementary preventive/early stage treatment agent for mesothelioma. This phase II clinical study then was conducted in 18 male-patients with evidence of radiographic characteristics related to asbestos exposure such as asbestosis or benign pleural disease as surrogate disease for mesothelioma clinical model.

RESULTS

We investigate AWPC biological activity assessing its effect on mesothelin serum level, a glycoprotein with low expression in normal mesothelial cells and high expression in mesothelioma and asbestos related diseases. We also assess the AWPC effect on circulating miRNAs, as novel biomarkers of both cancer risk and response to therapeutic targets. While we found a small and not significant effect of AWPC on mesothelin serum levels, we observed that AWPC intake modulated 11 serum miRNAs related to gene-pathways connected to mesothelioma etiology and development. In terms of toxicity, we also did not observe any severe adverse effects associated to AWPC treatment, only gastro-intestinal symptoms were reported by five study participants.

CONCLUSIONS

We observed an interesting AWPC effect on miRNAs which targets modulate mesothelioma development. New and much larger clinical studies based on follow-up of workers exposed to asbestos are needed to corroborate the role of AWPC in prevention and early treatment of mesothelioma.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT02076672 . Registered 03/03/2014.

Address: Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy. [email protected].; Department of Oncology, McMaster University, Hamilton, ON, Canada. [email protected].; Biostatistics and Bioinformatics, UOSD Clinical Trial Center, IRCCS Regina Elena National Cancer Institute, Rome, Italy.; Translational Oncology Research Unit, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS, Regina Elena National Cancer Institute, Rome, Italy.; Scientific Direction Office, IRCSS San Gallicano Dermatological Institute, Rome, Italy.; Department of Oncology, McMaster University, Hamilton, ON, Canada.; Juravinski Cancer Center, Hamilton Health Science, Hamilton, ON, Canada.; Ontario Clinical Oncology Group, Hamilton, ON, Canada.; Department of Medicine, McMaster University, Hamilton, ON, Canada.; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.; SAFU Laboratory, Department of Research, Advanced Diagnostic, and Technological Innovation, IRCCS Regina Elena National Cancer Institute, Rome, Italy.

DOI: 10.1186/s13046-022-02455-6

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MeSH Terms: Asbestos, Biomarkers, Tumor, Cynara scolymus, GPI-Linked Proteins, Humans, Lung Neoplasms, Male, Mesothelin, Mesothelioma, Mesothelioma, Malignant, MicroRNAs, Pleural Neoplasms