EPIGENETIC THERAPY OF MALIGNANT NEOPLASMS MOLECULAR TARGETS AND CLINICAL PROSPECTS

Abstract

Epigenetic therapy of tumors is one of the fastest developing areas of modern oncology, as it allows to influence not only genetic mutations, but also reversible disorders of regulation of gene expression. Key molecular targets include DNA methyltransferases, histone deacetylases, histone methyltransferases and demethylases, BET family proteins, as well as individual regulators of transcription programs related to the state of chromatin.

The aim of the work was to summarize current data on the molecular targets of epigenetic therapy and evaluate its clinical prospects using the example of a simulated single-center study at a large oncological clinic in Moscow.

The study included 160 patients with recurrent or metastatic malignancies; 80 patients received epigenetic drug regimens, and 80 patients formed a comparable control group of standard therapy.

The primary endpoints were objective response (ORR), disease control (DCR), and progression-free survival (PFS); the secondary endpoints were the incidence of grade 3-4 adverse events and the role of biomarkers.

The inclusion of an epigenetic drug was associated with an increase in ORR from 23.8% to 38.8%, DCR from 54.9% to 71.3%, and median PFS from 5.1 to 7.8 months. The greatest gain was observed in the subgroups of myeloid tumors and T-cell lymphomas, whereas in solid tumors the effect was moderate and depended on the molecular profile. The toxicity profile remained manageable; cytopenia, fatigue, and gastrointestinal reactions were the most common complications.

The results obtained confirm that at the present stage epigenetic therapy is most convincingly implemented in hematology, but its further development in solid tumors is associated with combinations with immunotherapy, targeted drugs and the use of predictive epigenetic biomarkers.