Challenges in the detection of epigenetically active non-genotoxic carcinogens

Introduction. One of the reasons for the observed increase in the incidence of malignant neoplasms is the lack of control over the spread of non-genotoxic carcinogens. The purpose of this review is to analyze the problems in testing non-genotoxic carcinogens and ways to develop adequate approaches to their detection by analyzing the epigenetic activity of compounds.

Material and methods. The analysis of more than 200 scientific publications on the topic of detection of carcinogenic hazards has been carried out. The databases PubMed (149), Scopus (62), Web of Science (33), ResearchGate (15), RSCI (12) were used. Based on the analysis, 50 most informative publications reflecting the main aspects of the problem of testing non-genotoxic carcinogens have been selected.

Results. The article presents the problem of preventing carcinogenesis caused by non-genotoxic compounds, the relevance and scientific justification for testing these compounds, and discusses existing approaches to developing regulated control measures for non-genotoxic carcinogens. An author’s method for detecting epigenetically active compounds using genetically modified cellular systems with a reporter epigenetically suppressed fluorophore protein gene is proposed as an integral screening test for the potential effect of a compound on the system of epigenetic regulation of gene expression.

Limitations. The study is based on an analysis of open data on testing of genotoxic and non-genotoxic compounds in the aforementioned databases.

Conclusion. The data confirming the relevance and necessity of testing non-genotoxic carcinogens, existing challenges and ways to solve problems in the field of preventing the incidence of malignant neoplasms are systematically reviewed.

Compliance with ethical standards. The opinion of the Bioethics Commission is not required.

Authors’ contribution:
Yakubovskaya M.G. – concept and design of the study, writing, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article;
Maksimova V.P. – collection and processing of the material, writing the text for testing epigenetically active compounds, editing;
Belitsky G.A. – writing the text, editing, approval of the final version;
Kirsanov K.I. – research concept and design, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The research was supported by the Russian Science Foundation, grant No. 25-15-00432.

Received: December 24, 2025 / Revised: January 12, 2026 / Accepted: February 2, 2026 / Published: March 18, 2026

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