基于基因组的个性化化疗分析支持乳腺癌决策系统

Aydin Saribudak, S. Gundry, Jianmin Zou, M. U. Uyar
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引用次数: 9

摘要

个性化的抗癌治疗方法需要针对个别癌症患者制定标准化的化疗计划指南。我们介绍了一种基于乳腺癌患者基因组数据的方法,即个性化相关参数化(PReP-G),来计算药物对肿瘤进展的疗效时间过程。通过计算运输隔室系统的药效学(PD)参数来量化药物疗效和细胞死亡动力学。我们将来自I-SPY 1试验的78例临床t期为3的患者的74个乳腺癌相关基因的遗传信息与NBIA数据库的肿瘤体积测量数据整合到我们的PReP-G模型中,以计算肿瘤的生长和收缩参数。对给定化疗时间的BT-474、MDA-MB-435和MDA-MB-231乳腺癌细胞系进行性能评价,其中给药动物模型使用抗癌药物阿霉素和环磷酰胺,及时测量肿瘤大小的变化。我们将p - g模型计算结果与实验测量结果进行了比较。计算结果和体积测量之间的一致性鼓舞了基于遗传数据开发个性化肿瘤生长模型和决策支持系统。
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Genomic based personalized chemotherapy analysis to support decision systems for breast cancer
Personalized approach to anti-cancer therapy necessitates the adaptation of standardized guidelines for chemotherapy schedules to individual cancer patients. We introduce a methodology, namely Personalized Relevance Parameterization (PReP-G), based on the genomic data of breast cancer patients to compute time course of drug efficacy on tumor progression. The pharmacodynamic (PD) parameters of transit compartmental systems are computed to quantify the drug efficacy and kinetics of cell death. We integrate the genetic information of 74 breast cancer related genes for 78 patients with clinical t-stage of 3 from the I-SPY 1 TRIAL with the tumor volume measurements from NBIA database into our PReP-G model to compute tumor growth and shrinkage parameters. The performance of the method is evaluated for the breast cancer cell lines of BT-474, MDA-MB-435 and MDA-MB-231 for a given chemotherapy, where the anti-cancer agents Doxorubicin and Cyclophosphamide are administered to animal models and the change of tumor size is measured in time. We compare our results from PReP-G model with the experimental measurements. The consistency between computed results and the volume measurements is encouraging to develop personalized tumor growth models and decision support systems based on genetic data.
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