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

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.