美国食品和药物管理局批准的细胞毒药物的药物基因组学特征。
Pharmacogenomic characterization of US FDA-approved cytotoxic drugs.
机构信息
UNC Institute for Pharmacogenomics & Individualized Therapy, University of North Carolina, Chapel Hill, NC 27599-7361, USA.
出版信息
Pharmacogenomics. 2011 Oct;12(10):1407-15. doi: 10.2217/pgs.11.92.
Abstract
AIMS
Individualization of cancer chemotherapy based on the patient's genetic makeup holds promise for reducing side effects and improving efficacy. However, the relative contribution of genetics to drug response is unknown.
MATERIALS & METHODS: In this study, we investigated the cytotoxic effect of 29 commonly prescribed chemotherapeutic agents from diverse drug classes on 125 lymphoblastoid cell lines derived from 14 extended families.
RESULTS
The results of this systematic study highlight the variable role that genetics plays in response to cytotoxic drugs, ranging from a heritability of <0.15 for gemcitabine to >0.60 for epirubicin.
CONCLUSION
Putative quantitative trait loci for cytotoxic response were identified, as well as drug class-specific signatures, which could indicate possible shared genetic mechanisms. In addition to the identification of putative quantitative trait locis, the results of this study inform the prioritization of chemotherapeutic drugs with a sizable genetic response component for future investigation.
摘要
目的
基于患者的基因构成对癌症化疗进行个体化治疗有望减少副作用并提高疗效。然而，遗传因素对药物反应的相对贡献尚不清楚。
材料与方法
在这项研究中，我们研究了来自 14 个扩展家族的 125 个淋巴母细胞系对 29 种常用化疗药物的细胞毒性作用。
结果
这项系统研究的结果突出了遗传因素在细胞毒性药物反应中的不同作用，从吉西他滨的遗传率<0.15 到表柔比星的遗传率>0.60 不等。
结论
确定了细胞毒性反应的推定数量性状基因座，以及药物类别特异性特征，这可能表明存在可能的共享遗传机制。除了鉴定推定的数量性状基因座外，本研究的结果还为具有相当大遗传反应成分的化疗药物的未来研究提供了信息，以确定优先次序。
相似文献
1
Pharmacogenomic characterization of US FDA-approved cytotoxic drugs.美国食品和药物管理局批准的细胞毒药物的药物基因组学特征。
Pharmacogenomics. 2011 Oct;12(10):1407-15. doi: 10.2217/pgs.11.92.
2
Protein quantitative trait loci identify novel candidates modulating cellular response to chemotherapy.蛋白质数量性状基因座鉴定出调节细胞对化疗反应的新候选基因。
PLoS Genet. 2014 Apr 3;10(4):e1004192. doi: 10.1371/journal.pgen.1004192. eCollection 2014 Apr.
4
Large-Scale Drug Screening in Patient-Derived IDH Glioma Stem Cells Identifies Several Efficient Drugs among FDA-Approved Antineoplastic Agents.在患者来源的 IDH 神经胶质瘤干细胞中进行大规模药物筛选，在 FDA 批准的抗肿瘤药物中鉴定出几种有效药物。
Cells. 2020 Jun 3;9(6):1389. doi: 10.3390/cells9061389.
5
Chemotherapeutic-induced apoptosis: a phenotype for pharmacogenomics studies.化疗诱导细胞凋亡：药物基因组学研究的表型。
Pharmacogenet Genomics. 2011 Aug;21(8):476-88. doi: 10.1097/FPC.0b013e3283481967.
6
Genome-wide discovery of loci influencing chemotherapy cytotoxicity.全基因组范围内影响化疗细胞毒性的基因座发现
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11809-14. doi: 10.1073/pnas.0404580101. Epub 2004 Jul 28.
7
Use of cell lines in the investigation of pharmacogenetic loci.细胞系在药物遗传学基因座研究中的应用。
Curr Pharm Des. 2009;15(32):3782-95. doi: 10.2174/138161209789649475.
8
Pharmacogenomic biomarker information in FDA-approved paediatric drug labels.美国食品药品监督管理局批准的儿科药物标签中的药物基因组生物标志物信息。
Basic Clin Pharmacol Toxicol. 2015 May;116(5):438-44. doi: 10.1111/bcpt.12341. Epub 2014 Nov 21.
9
Study of pharmacogenomic information in FDA-approved drug labeling to facilitate application of precision medicine.研究 FDA 批准药物标签中的药物基因组学信息，以促进精准医学的应用。
Drug Discov Today. 2020 May;25(5):813-820. doi: 10.1016/j.drudis.2020.01.023. Epub 2020 Feb 4.
10
Novel anti-glioblastoma agents and therapeutic combinations identified from a collection of FDA approved drugs.从美国食品和药物管理局批准的药物集中鉴定出新型抗神经胶质瘤药物和治疗组合。
J Transl Med. 2014 Jan 17;12:13. doi: 10.1186/1479-5876-12-13.
引用本文的文献
1
Pharmacogenomic Analyses Implicate B Cell Developmental Status and as Determinants of Sensitivity toward Anti-CD20 Monoclonal Antibody Therapy.药物基因组学分析提示 B 细胞发育状态和 是抗 CD20 单克隆抗体治疗敏感性的决定因素。
Cells. 2023 Jun 7;12(12):1574. doi: 10.3390/cells12121574.
2
Cardiovascular Health Status And Genetic Risk In Survivors of Childhood Neuroblastoma and Nephroblastoma Treated With Doxorubicin: Protocol of the Pharmacogenetic Part of the LESS-Anthra Cross-Sectional Cohort Study.接受阿霉素治疗的儿童神经母细胞瘤和肾母细胞瘤幸存者的心血管健康状况及遗传风险：LESS-蒽环类药物横断面队列研究的药物遗传学部分方案
JMIR Res Protoc. 2022 Feb 17;11(2):e27898. doi: 10.2196/27898.
3
High-throughput screening and genome-wide analyses of 44 anticancer drugs in the 1000 Genomes cell lines reveals an association of the NQO1 gene with the response of multiple anticancer drugs.高通量筛选和全基因组分析 1000 个基因组细胞系中的 44 种抗癌药物，揭示了 NQO1 基因与多种抗癌药物反应的关联。
PLoS Genet. 2021 Aug 26;17(8):e1009732. doi: 10.1371/journal.pgen.1009732. eCollection 2021 Aug.
4
The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?结直肠癌药物基因组学的现状：我们离个性化治疗更近了吗？
J Pers Med. 2020 Nov 19;10(4):237. doi: 10.3390/jpm10040237.
5
Synergistic Chemotherapy Drug Response Is a Genetic Trait in Lymphoblastoid Cell Lines.协同化疗药物反应是淋巴母细胞系中的一种遗传特性。
Front Genet. 2019 Oct 15;10:829. doi: 10.3389/fgene.2019.00829. eCollection 2019.
6
Concomitant Medications and Risk of Chemotherapy-Induced Peripheral Neuropathy.伴随药物与化疗引起的周围神经病风险。
Oncologist. 2019 Aug;24(8):e784-e792. doi: 10.1634/theoncologist.2018-0418. Epub 2018 Nov 23.
7
The influence of Neanderthal alleles on cytotoxic response.尼安德特人基因对细胞毒性反应的影响。
PeerJ. 2018 Oct 23;6:e5691. doi: 10.7717/peerj.5691. eCollection 2018.
8
Gene expression and linkage analysis implicate CBLB as a mediator of rituximab resistance.基因表达和连锁分析表明CBLB是利妥昔单抗耐药性的一个介导因子。
Pharmacogenomics J. 2018 May 22;18(3):467-473. doi: 10.1038/tpj.2017.41. Epub 2017 Dec 5.
9
An Introduction to Terminology and Methodology of Chemical Synergy-Perspectives from Across Disciplines.化学协同作用的术语和方法导论——跨学科视角
Front Pharmacol. 2017 Apr 20;8:158. doi: 10.3389/fphar.2017.00158. eCollection 2017.
10
Evaluating the role of admixture in cancer therapy via in vitro drug response and multivariate genome-wide associations.通过体外药物反应和多变量全基因组关联评估混合在癌症治疗中的作用。
Pharmacogenomics. 2015;16(13):1451-63. doi: 10.2217/PGS.15.85. Epub 2015 Aug 28.
本文引用的文献
1
Genetic analysis of radiation-induced changes in human gene expression.辐射诱导的人类基因表达变化的遗传分析。
Nature. 2009 May 28;459(7246):587-91. doi: 10.1038/nature07940. Epub 2009 Apr 6.
2
Genetic analysis of human traits in vitro: drug response and gene expression in lymphoblastoid cell lines.人类性状的体外遗传分析：淋巴母细胞系中的药物反应和基因表达
PLoS Genet. 2008 Nov;4(11):e1000287. doi: 10.1371/journal.pgen.1000287. Epub 2008 Nov 28.
3
Cancer pharmacogenomics: DNA genotyping and gene expression profiling to identify molecular determinants of chemosensitivity.癌症药物基因组学：DNA基因分型与基因表达谱分析以确定化学敏感性的分子决定因素。
Drug Metab Rev. 2008;40(2):303-15. doi: 10.1080/03602530801952427.
4
A HapMap harvest of insights into the genetics of common disease.从HapMap中获取对常见疾病遗传学的深刻见解。
J Clin Invest. 2008 May;118(5):1590-605. doi: 10.1172/JCI34772.
5
Identification of genetic variants contributing to cisplatin-induced cytotoxicity by use of a genomewide approach.利用全基因组方法鉴定导致顺铂诱导细胞毒性的基因变异。
Am J Hum Genet. 2007 Sep;81(3):427-37. doi: 10.1086/519850. Epub 2007 Aug 1.
6
Mapping genes that contribute to daunorubicin-induced cytotoxicity.定位与柔红霉素诱导的细胞毒性相关的基因。
Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.
7
A genome-wide approach to identify genetic variants that contribute to etoposide-induced cytotoxicity.一种全基因组方法，用于鉴定导致依托泊苷诱导的细胞毒性的遗传变异。
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9758-63. doi: 10.1073/pnas.0703736104. Epub 2007 May 30.
8
The cancer and leukemia group B pharmacology and experimental therapeutics committee: a historical perspective.癌症与白血病B组药理学与实验治疗学委员会：历史视角
Clin Cancer Res. 2006 Jun 1;12(11 Pt 2):3612s-6s. doi: 10.1158/1078-0432.CCR-06-9008.
9
Genome-wide discovery of loci influencing chemotherapy cytotoxicity.全基因组范围内影响化疗细胞毒性的基因座发现
Proc Natl Acad Sci U S A. 2004 Aug 10;101(32):11809-14. doi: 10.1073/pnas.0404580101. Epub 2004 Jul 28.
10
Natural variation in human gene expression assessed in lymphoblastoid cells.在淋巴母细胞中评估的人类基因表达的自然变异。
Nat Genet. 2003 Mar;33(3):422-5. doi: 10.1038/ng1094. Epub 2003 Feb 3.
Zotero 插件