• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

生物信息学分析将基因组缺陷与化疗敏感性和作用机制联系起来。

Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.

机构信息

Information Technologies Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD, United States of America.

出版信息

PLoS One. 2021 Apr 28;16(4):e0243336. doi: 10.1371/journal.pone.0243336. eCollection 2021.

DOI:10.1371/journal.pone.0243336
PMID:33909629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8081165/
Abstract

A joint analysis of the NCI60 small molecule screening data, their genetically defective genes, and mechanisms of action (MOA) of FDA approved cancer drugs screened in the NCI60 is proposed for identifying links between chemosensitivity, genomic defects and MOA. Self-Organizing-Maps (SOMs) are used to organize the chemosensitivity data. Student's t-tests are used to identify SOM clusters with enhanced chemosensitivity for tumor cell lines with versus without genetically defective genes. Fisher's exact and chi-square tests are used to reveal instances where defective gene to chemosensitivity associations have enriched MOAs. The results of this analysis find a relatively small set of defective genes, inclusive of ABL1, AXL, BRAF, CDC25A, CDKN2A, IGF1R, KRAS, MECOM, MMP1, MYC, NOTCH1, NRAS, PIK3CG, PTK2, RPTOR, SPTBN1, STAT2, TNKS and ZHX2, as possible candidates for roles in chemosensitivity for compound MOAs that target primarily, but not exclusively, kinases, nucleic acid synthesis, protein synthesis, apoptosis and tubulin. These results find exploitable instances of enhanced chemosensitivity of compound MOA's for selected defective genes. Collectively these findings will advance the interpretation of pre-clinical screening data as well as contribute towards the goals of cancer drug discovery, development decision making, and explanation of drug mechanisms.

摘要

建议对 NCI60 小分子筛选数据、其遗传缺陷基因以及在 NCI60 中筛选的 FDA 批准的癌症药物的作用机制 (MOA) 进行联合分析，以确定化学敏感性、基因组缺陷和 MOA 之间的联系。使用自组织图 (SOM) 对化学敏感性数据进行组织。使用学生 t 检验来识别具有遗传缺陷基因的肿瘤细胞系与没有遗传缺陷基因的肿瘤细胞系相比具有增强化学敏感性的 SOM 簇。使用 Fisher 精确检验和卡方检验来揭示缺陷基因与化学敏感性关联具有丰富 MOA 的情况。该分析的结果发现了一组相对较少的缺陷基因，包括 ABL1、AXL、BRAF、CDC25A、CDKN2A、IGF1R、KRAS、MECOM、MMP1、MYC、NOTCH1、NRAS、PIK3CG、PTK2、RPTOR、SPTBN1、STAT2、TNKS 和 ZHX2，它们可能作为针对主要但不限于激酶、核酸合成、蛋白质合成、细胞凋亡和微管的化合物 MOA 的化学敏感性的候选物。这些结果发现了针对选定缺陷基因的化合物 MOA 增强化学敏感性的可利用实例。这些发现将共同推进对临床前筛选数据的解释，并有助于癌症药物发现、开发决策以及药物机制的解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/93a9a1a403fd/pone.0243336.g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/19def2cf3f40/pone.0243336.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/ce38151196cf/pone.0243336.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/c89747dae814/pone.0243336.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/5227f84774fb/pone.0243336.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/4d07333cd688/pone.0243336.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/2dc463cdb128/pone.0243336.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/016fab318cbe/pone.0243336.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/aec7a3a78006/pone.0243336.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/aaf8a144e814/pone.0243336.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/90c2372e2629/pone.0243336.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/007906f9555d/pone.0243336.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/e6360276cbd9/pone.0243336.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/31ed12650a98/pone.0243336.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/14c1e37bd246/pone.0243336.g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/93a9a1a403fd/pone.0243336.g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/19def2cf3f40/pone.0243336.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/ce38151196cf/pone.0243336.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/c89747dae814/pone.0243336.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/5227f84774fb/pone.0243336.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/4d07333cd688/pone.0243336.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/2dc463cdb128/pone.0243336.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/016fab318cbe/pone.0243336.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/aec7a3a78006/pone.0243336.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/aaf8a144e814/pone.0243336.g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/90c2372e2629/pone.0243336.g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/007906f9555d/pone.0243336.g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/e6360276cbd9/pone.0243336.g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/31ed12650a98/pone.0243336.g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/14c1e37bd246/pone.0243336.g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0278/8081165/93a9a1a403fd/pone.0243336.g015.jpg

相似文献

1
Bioinformatic analysis linking genomic defects to chemosensitivity and mechanism of action.生物信息学分析将基因组缺陷与化疗敏感性和作用机制联系起来。
PLoS One. 2021 Apr 28;16(4):e0243336. doi: 10.1371/journal.pone.0243336. eCollection 2021.
2
Prediction of drug efficacy for cancer treatment based on comparative analysis of chemosensitivity and gene expression data.基于化疗敏感性和基因表达数据的比较分析预测癌症治疗的药物疗效。
Bioorg Med Chem. 2012 Jan 1;20(1):167-76. doi: 10.1016/j.bmc.2011.11.019. Epub 2011 Nov 22.
3
Integrating constitutive gene expression and chemoactivity: mining the NCI60 anticancer screen.整合组成型基因表达和化疗活性：挖掘 NCI60 抗癌筛选。
PLoS One. 2012;7(10):e44631. doi: 10.1371/journal.pone.0044631. Epub 2012 Oct 2.
4
Chemosensitivity profile of cancer cell lines and identification of genes determining chemosensitivity by an integrated bioinformatical approach using cDNA arrays.癌细胞系的化学敏感性概况以及通过使用cDNA阵列的综合生物信息学方法鉴定决定化学敏感性的基因。
Mol Cancer Ther. 2005 Mar;4(3):399-412. doi: 10.1158/1535-7163.MCT-04-0234.
5
An integrative genomic and proteomic approach to chemosensitivity prediction.一种用于化疗敏感性预测的综合基因组和蛋白质组学方法。
Int J Oncol. 2009 Jan;34(1):107-15. doi: 10.3892/ijo_00000134.
6
Identification of selective cytotoxic and synthetic lethal drug responses in triple negative breast cancer cells.三阴性乳腺癌细胞中选择性细胞毒性和合成致死性药物反应的鉴定。
Mol Cancer. 2016 May 10;15(1):34. doi: 10.1186/s12943-016-0517-3.
7
Linking the growth inhibition response from the National Cancer Institute's anticancer screen to gene expression levels and other molecular target data.将美国国立癌症研究所抗癌筛选的生长抑制反应与基因表达水平及其他分子靶点数据相联系。
Bioinformatics. 2003 Nov 22;19(17):2212-24. doi: 10.1093/bioinformatics/btg302.
8
In vitro pharmacogenomic database and chemosensitivity predictive genes in gastric cancer.胃癌的体外药物基因组数据库及化疗敏感性预测基因
Genomics. 2009 Jan;93(1):52-61. doi: 10.1016/j.ygeno.2008.08.002. Epub 2008 Oct 22.
9
Genes regulating the sensitivity of solid tumor cell lines to cytotoxic agents: a literature review.调控实体瘤细胞系对细胞毒性药物敏感性的基因：文献综述
Jpn J Clin Oncol. 2007 May;37(5):329-36. doi: 10.1093/jjco/hym035.
10
Correlation of gene expression and associated mutation profiles of APOBEC3A, APOBEC3B, REV1, UNG, and FHIT with chemosensitivity of cancer cell lines to drug treatment.APOBEC3A、APOBEC3B、REV1、UNG 和 FHIT 的基因表达与突变谱与癌细胞系对药物治疗的化疗敏感性的相关性。
Hum Genomics. 2018 Apr 11;12(1):20. doi: 10.1186/s40246-018-0150-x.

本文引用的文献

1
Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns.基于驱动突变共发生模式的个体化癌症治疗优先级排序。
Genome Med. 2020 Sep 9;12(1):78. doi: 10.1186/s13073-020-00774-x.
2
Identification of MMP1 as a potential gene conferring erlotinib resistance in non-small cell lung cancer based on bioinformatics analyses.基于生物信息学分析鉴定 MMP1 为非小细胞肺癌中厄洛替尼耐药的潜在基因。
Hereditas. 2020 Jul 23;157(1):32. doi: 10.1186/s41065-020-00145-x.
3
The PI3K-AKT-mTOR Pathway and Prostate Cancer: At the Crossroads of AR, MAPK, and WNT Signaling.
PI3K-AKT-mTOR 通路与前列腺癌：AR、MAPK 和 WNT 信号的十字路口。
Int J Mol Sci. 2020 Jun 25;21(12):4507. doi: 10.3390/ijms21124507.
4
Discovering the anti-cancer potential of non-oncology drugs by systematic viability profiling.通过系统生存力分析发现非肿瘤药物的抗癌潜力。
Nat Cancer. 2020 Feb;1(2):235-248. doi: 10.1038/s43018-019-0018-6. Epub 2020 Jan 20.
5
CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT/mTOR pathway.CDKN2A 通过 LDHA 介导的 AKT/mTOR 通路抑制宫颈癌中的细胞增殖和侵袭。
Clin Transl Oncol. 2021 Feb;23(2):222-228. doi: 10.1007/s12094-020-02409-4. Epub 2020 Jun 27.
6
Current therapy of KRAS-mutant lung cancer.KRAS 突变型肺癌的当前治疗方法。
Cancer Metastasis Rev. 2020 Dec;39(4):1159-1177. doi: 10.1007/s10555-020-09903-9.
7
Dual Targeting of BRAF and mTOR Signaling in Melanoma Cells with Pyridinyl Imidazole Compounds.用吡啶基咪唑化合物对黑色素瘤细胞中的BRAF和mTOR信号进行双重靶向作用
Cancers (Basel). 2020 Jun 10;12(6):1516. doi: 10.3390/cancers12061516.
8
Single-cell RNA sequencing demonstrates the molecular and cellular reprogramming of metastatic lung adenocarcinoma.单细胞 RNA 测序显示转移性肺腺癌的分子和细胞重编程。
Nat Commun. 2020 May 8;11(1):2285. doi: 10.1038/s41467-020-16164-1.
9
Differential Expression and Alternative Splicing of Transcripts Associated With Cisplatin-Induced Chemoresistance in Nasopharyngeal Carcinoma.鼻咽癌中与顺铂诱导的化疗耐药相关转录本的差异表达和可变剪接
Front Genet. 2020 Feb 25;11:52. doi: 10.3389/fgene.2020.00052. eCollection 2020.
10
Destruction of a Microtubule-Bound MYC Reservoir during Mitosis Contributes to Vincristine's Anticancer Activity.有丝分裂期间微管结合型 MYC 库的破坏有助于长春新碱的抗癌活性。
Mol Cancer Res. 2020 Jun;18(6):859-872. doi: 10.1158/1541-7786.MCR-19-1203. Epub 2020 Mar 11.