Growth rate inhibition metrics correct for confounders in measuring sensitivity to cancer drugs

药物发现 药品 计算生物学 灵敏度(控制系统) 生长抑制 生物 生物标志物发现 细胞生长 药理学 生物信息学 遗传学 基因 蛋白质组学 电子工程 工程类
作者
Marc Hafner,Mario Niepel,Mirra Chung,Peter K. Sorger
出处
期刊:Nature Methods [Springer Nature]
卷期号:13 (6): 521-527 被引量:559
标识
DOI:10.1038/nmeth.3853
摘要

Growth inhibition metrics allow for robust measurement of drug efficacy independent of variables such as cell growth rate, seeding density, and growth medium; they are a practical alternative to metrics such as IC50 and offer enhanced reproducibility. Drug sensitivity and resistance are conventionally quantified by IC50 or Emax values, but these metrics are highly sensitive to the number of divisions taking place over the course of a response assay. The dependency of IC50 and Emax on division rate creates artefactual correlations between genotype and drug sensitivity, while obscuring valuable biological insights and interfering with biomarker discovery. We derive alternative small molecule drug-response metrics that are insensitive to division number. These are based on estimation of the magnitude of drug-induced growth rate inhibition (GR) using endpoint or time-course assays. We show that GR50 and GRmax are superior to conventional metrics for assessing the effects of small molecule drugs in dividing cells. Moreover, adopting GR metrics requires only modest changes in experimental protocols. We expect GR metrics to improve the study of cell signaling and growth using small molecules and biologics and to facilitate the discovery of drug-response biomarkers and the identification of drugs effective against specific patient-derived tumor cells.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
顾矜应助gyhk采纳,获得10
刚刚
surfing完成签到,获得积分10
刚刚
1秒前
1秒前
fancyyyy完成签到,获得积分10
2秒前
小李给我支棱起来完成签到,获得积分10
2秒前
daoyi应助王某采纳,获得10
3秒前
复杂颦完成签到,获得积分10
3秒前
syangZ完成签到,获得积分10
3秒前
科研通AI5应助花纸鸳采纳,获得10
4秒前
4秒前
4秒前
科研通AI5应助大方弘文采纳,获得10
4秒前
chenjun7080发布了新的文献求助30
5秒前
美好幻灵发布了新的文献求助10
6秒前
6秒前
6秒前
科研通AI5应助盛夏如花采纳,获得10
8秒前
AbMole_小智完成签到,获得积分10
8秒前
医生发布了新的文献求助10
8秒前
9秒前
阿玖完成签到 ,获得积分10
9秒前
吃大肉完成签到,获得积分10
10秒前
10秒前
10秒前
10秒前
淡淡夕阳完成签到,获得积分10
11秒前
BFQQQQ发布了新的文献求助10
11秒前
11秒前
11秒前
13秒前
syangZ完成签到,获得积分10
13秒前
14秒前
14秒前
胡不喜完成签到,获得积分10
14秒前
15秒前
Catalina_S应助科研通管家采纳,获得20
16秒前
xiaolianwheat发布了新的文献求助10
16秒前
脑洞疼应助科研通管家采纳,获得10
16秒前
搜集达人应助医生采纳,获得10
16秒前
高分求助中
Production Logging: Theoretical and Interpretive Elements 2700
Mechanistic Modeling of Gas-Liquid Two-Phase Flow in Pipes 2500
Kelsen’s Legacy: Legal Normativity, International Law and Democracy 1000
Handbook on Inequality and Social Capital 800
Conference Record, IAS Annual Meeting 1977 610
Interest Rate Modeling. Volume 3: Products and Risk Management 600
Interest Rate Modeling. Volume 2: Term Structure Models 600
热门求助领域 (近24小时)
化学 材料科学 生物 医学 工程类 有机化学 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 基因 遗传学 物理化学 催化作用 量子力学 光电子学 冶金
热门帖子
关注 科研通微信公众号,转发送积分 3546815
求助须知:如何正确求助?哪些是违规求助? 3123829
关于积分的说明 9357111
捐赠科研通 2822447
什么是DOI,文献DOI怎么找? 1551477
邀请新用户注册赠送积分活动 723475
科研通“疑难数据库(出版商)”最低求助积分说明 713766