Kalamara Angeliki, Tobalina Luis, Saez-Rodriguez Julio
RWTH Aachen University, Faculty of Medicine, Joint Research Centre for Computational Biomedicine, Aachen, Germany.
European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, UK.
Curr Opin Syst Biol. 2018 Aug;10:53-62. doi: 10.1016/j.coisb.2018.07.001.
Cancer is a highly heterogeneous disease with complex underlying biology. For these reasons, effective cancer treatment is still a challenge. Nowadays, it is clear that a cancer therapy that fits all the cases cannot be found, and as a result the design of therapies tailored to the patient's molecular characteristics is needed. Pharmacogenomics aims to study the relationship between an individual's genotype and drug response. Scientists use different biological models, ranging from cell lines to mouse models, as proxies for patients for preclinical and translational studies. The rapid development of "-omics" technologies is increasing the amount of features that can be measured in these models, expanding the possibilities of finding predictive biomarkers of drug response. Finding these relationships requires diverse computational approaches ranging from machine learning to dynamic modeling. Despite major advances, we are still far from being able to precisely predict drug efficacy in cancer models, let alone directly on patients. We believe that the new experimental techniques and computational approaches covered in this review will bring us closer to this goal.
癌症是一种具有复杂潜在生物学特性的高度异质性疾病。由于这些原因,有效的癌症治疗仍然是一项挑战。如今,很明显找不到适用于所有病例的癌症治疗方法,因此需要设计针对患者分子特征的个性化治疗方案。药物基因组学旨在研究个体基因型与药物反应之间的关系。科学家们使用从细胞系到小鼠模型等不同的生物学模型,作为临床前和转化研究中患者的替代物。“组学”技术的快速发展正在增加这些模型中可测量的特征数量,扩大了寻找药物反应预测生物标志物的可能性。找到这些关系需要从机器学习到动态建模等多种计算方法。尽管取得了重大进展,但我们距离能够在癌症模型中精确预测药物疗效仍有很大差距——更不用说直接在患者身上进行预测了。我们相信,本综述中涵盖的新实验技术和计算方法将使我们更接近这一目标。