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超越靶向治疗的局限:将基因组数据与机器学习相结合,改善靶向药物的应用。

Beyond the limitation of targeted therapy: Improve the application of targeted drugs combining genomic data with machine learning.

机构信息

Faculty of Information Technology, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

Biological Engineering, Shanghai Jiao Tong University, 1954 Huashan Road, Xuhui District, Shanghai, China.

出版信息

Pharmacol Res. 2020 Sep;159:104932. doi: 10.1016/j.phrs.2020.104932. Epub 2020 May 28.

Abstract

Precision oncology involves effectively selecting drugs for cancer patients and planning an effective treatment regimen. However, for Molecular targeted drug, using genomic state of the drug target to select drugs has limitations. Many patients who could benefit from molecularly targeted drugs, but they are being missed due to the insufficient labelling ability of the existing target genes. For non-specific chemotherapy drugs, most of the first-line anticancer drugs do not have biomarkers to guide doctor make treatment regimen. Furthermore, it is important to determine a long-term treatment plan based on the patient's genomic data during tumor evolution. Therefore, it is necessary to establish a tumor drug sensitivity prediction model, which can assist doctors in designing a personalized tumor treatment regimen. This paper proposed a novel model to predict tumor drug sensitivity including targeted drugs and non-specific chemotherapy drugs. This model uses statistical methods based on Bimodal distribution to select multimodal genetic data to solve dimensional challenges and reduce noise and to establish a classification model to predict the effectiveness of the drug in the tumor cell line using machine learning. The experimental test 87 molecular targeted drugs and non-specific chemotherapy drugs. The results show that the method can effectively predict the sensitivity of tumor drugs with an average sensitivity of 0.98 and specificity of 0.97. This model is worth to promotion. If it can be successfully used in clinical trials, it will effectively assist doctors to develop personalized cancer treatment programs and expand the application of molecularly targeted drugs.

摘要

精准肿瘤学涉及有效地为癌症患者选择药物并制定有效的治疗方案。然而,对于分子靶向药物,使用药物靶点的基因组状态来选择药物存在局限性。许多可能受益于分子靶向药物的患者,但由于现有靶基因的标记能力不足而被忽略。对于非特异性化疗药物,大多数一线抗癌药物没有生物标志物来指导医生制定治疗方案。此外,在肿瘤进化过程中,根据患者的基因组数据确定长期治疗计划非常重要。因此,有必要建立一个肿瘤药物敏感性预测模型,以协助医生设计个性化的肿瘤治疗方案。本文提出了一种新的模型,可预测包括靶向药物和非特异性化疗药物在内的肿瘤药物敏感性。该模型使用基于双峰分布的统计方法来选择多峰遗传数据,以解决维度挑战并减少噪声,并使用机器学习建立分类模型来预测肿瘤细胞系中药物的疗效。该实验测试了 87 种分子靶向药物和非特异性化疗药物。结果表明,该方法可以有效地预测肿瘤药物的敏感性,平均敏感性为 0.98,特异性为 0.97。该模型值得推广。如果它能成功应用于临床试验,将有效帮助医生制定个性化的癌症治疗方案,并扩大分子靶向药物的应用。

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