Promises and challenges in pharmacoepigenetics.
Promises and challenges in pharmacoepigenetics.
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DOI：
10.1017/pcm.2023.6
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Altman, Russ B
中科院分区：
文献类型：
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作者：
Smith, Delaney A;Sadler, Marie C;Altman, Russ B
药物遗传学是研究个体间遗传差异如何影响药物反应的学科，它不能解释所有观察到的药物反应的遗传变异。表观遗传机制，如DNA甲基化和组蛋白乙酰化可能解释了一些无法解释的差异。表观遗传机制调节基因表达，可以成为合适的药物靶点，并可以影响非表观遗传药物的作用。药物表观遗传学是研究表观遗传变异与药物反应之间关系的领域。这些研究的大部分集中在靶向表观遗传机制的化合物上，称为表观遗传药物，用于治疗癌症，免疫紊乱和其他疾病。一些研究也表明表观遗传作用在经典的药物反应，但是，我们知道这方面的很少。由于技术进步，将表观遗传生物标志物与分子数据集相关联的信息量最近已经扩大，并且已经出现了新的计算方法来更好地识别和预测表观遗传相互作用。我们提出，表观遗传学和经典药物反应之间的关系可以使用现有的数据进行检查，通过（1）发现表观遗传变异的区域，（2）在这些区域内精确定位关键的表观遗传生物标志物，（3）将这些生物标志物映射到药物反应表型。这种方法扩展了现有的知识，以产生推定的药物表观遗传学关系，这可以通过实验进行测试。表观遗传修饰参与疾病和药物反应。因此，了解表观遗传驱动因素如何影响对经典药物的反应对于改善药物设计和管理以更好地治疗疾病非常重要。
Pharmacogenetics, the study of how interindividual genetic differences affect drug response, does not explain all observed heritable variance in drug response. Epigenetic mechanisms, such as DNA methylation, and histone acetylation may account for some of the unexplained variances. Epigenetic mechanisms modulate gene expression and can be suitable drug targets and can impact the action of nonepigenetic drugs. Pharmacoepigenetics is the field that studies the relationship between epigenetic variability and drug response. Much of this research focuses on compounds targeting epigenetic mechanisms, called epigenetic drugs, which are used to treat cancers, immune disorders, and other diseases. Several studies also suggest an epigenetic role in classical drug response; however, we know little about this area. The amount of information correlating epigenetic biomarkers to molecular datasets has recently expanded due to technological advances, and novel computational approaches have emerged to better identify and predict epigenetic interactions. We propose that the relationship between epigenetics and classical drug response may be examined using data already available by (1) finding regions of epigenetic variance, (2) pinpointing key epigenetic biomarkers within these regions, and (3) mapping these biomarkers to a drug-response phenotype. This approach expands on existing knowledge to generate putative pharmacoepigenetic relationships, which can be tested experimentally. Epigenetic modifications are involved in disease and drug response. Therefore, understanding how epigenetic drivers impact the response to classical drugs is important for improving drug design and administration to better treat disease.