# Impact of Tyrosine Kinase Inhibitors on the Expression Pattern of Epigenetic Regulators

## TL;DR

This study shows that tyrosine kinase inhibitors affect epigenetic regulators, which could help design better cancer treatments.

## Contribution

The study reveals how TKIs alter epigenetic regulators in cancers, offering new insights for combination therapies.

## Key findings

- TKI treatment significantly changes the expression of epigenetic writers, erasers, and readers in cancers.
- MicroRNAs and chromatin-remodeling complexes are also affected by TKI treatment.
- These findings suggest potential for combining TKIs with epigenetic drugs to improve cancer therapy.

## Abstract

Despite the emerging possibilities for personalized anticancer treatment, knowledge remains limited regarding the impact of distinct groups of targeted agents on the widespread network of signaling pathways and transcriptional regulatory mechanisms. The primary aim of this study was to evaluate how tyrosine kinase inhibitors (TKIs) influence the expression of epigenetic regulators through the analysis of Gene Expression Omnibus (GEO) datasets. Our results confirm numerous significant changes in the expression levels of epigenetic writers, erasers and readers as a consequence of TKI treatment in both hematological malignancies and solid tumors. These findings could facilitate further translational research aimed at establishing novel treatment combinations with enhanced antitumor efficacy in a personalized approach.

Background: Advances in molecular genetic diagnostics and emerging opportunities for targeted treatment have opened new horizons in precision oncology. Tyrosine kinase inhibitors (TKI) are the subgroup of these agents with which the most clinical experience has been gathered so far. However, little data is available on the effect of TKI agents on the expression levels of molecules responsible for epigenetic regulation. Methods: In this study, we investigated the effect of in vitro and in vivo treatment with tyrosine kinase inhibitor agents on the expression of epigenetic regulators in hematological malignancies and solid tumors, based on data included in the functional genomics repository Gene Expression Omnibus. Results: Statistical analysis of datasets and series of gene expression patterns revealed numerous significant changes in the levels of epigenetic writers, erasers, microRNAs and members of chromatin-remodeling complexes following TKI treatment. Previously published data about the role of these epigenetic modifiers in malignant diseases has also been summarized. Conclusions: Our results may contribute to the establishment of novel treatment strategies aiming at the combinatorial administration of TKI and epidrugs in cancer, leading to less toxic therapy with further improved results.