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.
背景：分子遗传学诊断技术的进步以及靶向治疗新机遇的出现，为精准肿瘤学开辟了新视野。酪氨酸激酶抑制剂（TKI）是目前临床经验积累最为丰富的靶向药物亚群。然而，关于TKI药物对表观遗传调控分子表达水平影响的数据仍较为有限。 方法：本研究基于功能基因组学数据库Gene Expression Omnibus收录的数据，探讨了酪氨酸激酶抑制剂在体外和体内治疗对血液系统恶性肿瘤及实体瘤中表观遗传调控因子表达的影响。 结果：通过对数据集及基因表达谱系列的统计分析，我们发现TKI治疗后表观遗传写入因子、擦除因子、微小RNA及染色质重塑复合物成员水平均发生显著变化。同时，本研究亦总结了已发表的关于这些表观遗传修饰因子在恶性疾病中作用的相关数据。 结论：我们的研究结果可能有助于建立TKI与表观遗传药物联合应用的新型癌症治疗策略，从而实现更低毒性、更优疗效的治疗方案。
Impact of Tyrosine Kinase Inhibitors on the Expression Pattern of Epigenetic Regulators
肿瘤(癌症)患者之家