Smith Delaney A, Sadler Marie C, Altman Russ B
Department of Bioengineering, Stanford University, Stanford, CA, USA.
University Center for Primary Care and Public Health, Lausanne, Switzerland.
Camb Prism Precis Med. 2023 Feb 9;1:e18. doi: 10.1017/pcm.2023.6. eCollection 2023.
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.
药物遗传学研究个体间基因差异如何影响药物反应，但无法解释所有观察到的药物反应遗传变异。表观遗传机制，如DNA甲基化和组蛋白乙酰化，可能是部分无法解释的变异的原因。表观遗传机制调节基因表达，可能是合适的药物靶点，并能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。这项研究大多聚焦于针对表观遗传机制的化合物，即表观遗传药物，这些药物用于治疗癌症、免疫紊乱及其他疾病。多项研究还表明表观遗传学在经典药物反应中发挥作用；然而，我们对该领域了解甚少。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有所增加，并且出现了新的计算方法以更好地识别和预测表观遗传相互作用。我们建议，可以利用现有数据，通过以下方式研究表观遗传学与经典药物反应之间的关系：（1）找到表观遗传变异区域，（2）确定这些区域内的关键表观遗传生物标志物，（3）将这些生物标志物与药物反应表型进行映射。这种方法在现有知识基础上拓展，以产生可能的药物表观遗传学关系，可通过实验进行验证。表观遗传修饰与疾病和药物反应有关。因此，了解表观遗传驱动因素如何影响对经典药物的反应，对于改进药物设计和给药以更好地治疗疾病至关重要。
